Kashin-Beck Disease
Encyclopedia
Kashin-Beck disease is a chronic, endemic osteochondropathy
(disease of the bone), which is mainly distributed from northeastern to southwestern China involving 15 provinces (Yao, Pei and Kang, 2011, p.1095-1100). Tibet currently has the highest incidence rate of KBD in China (Yao, et al). Southeast Siberia and North Korea are also other affected areas (Yao, et al). KBD usually involves children aged 5-15, and to date more than a million individuals have suffered from KBD (Wang, Fu, Shi, and Wang, 2011, p. 502-507). The symptoms of KBD include joint pain, morning stiffness in the joints, disturbances of flexion and extension in the elbows, enlarged inter-phalangeal joints and limited motion in many joints of the body (Cao, Li, Shi, Yue, Sun, Chen, Fu, Hughes and Caterson, 2008, p.680-688). Death of cartilage cells in the growth plate and articular surface is the basic pathologic feature; this can result in growth retardation and secondary osteoarthrosis (Yao, et al). Histological diagnosis of KBD is particularly difficult, clinical and radiological examinations have proved to be the best means for identifying KBD (Xiong, 2001, p.147-150). Little is known about the early stages of KBD before the visible appearance of the disease becomes evident in the destruction of the joints (Xiong, 2001, p.147-150).
This disease has been recognized for over 150 years but its etiology
has not yet been completely defined (Yao, et al.) Currently the accepted potential causes of KBD include mycotoxins present in grain, trace mineral deficiency in nutrition and high levels of fulvic acid in drinking water (Yao, et al). Selenium and iodine have been considered the most important deficiencies associated with KBD (Yao, et al). Mycotoxins produced by fungi can contaminate grain which may cause KBD because mycotoxins cause the production of free radicals (Yao, et al). T-2 is the mycotoxin implicated with KBD, produced by members of several fungal genera (Wang, et al). T-2 toxin can cause lesions in hematopoietic, lymphoid
, gastrointestinal, and cartilage tissues, especially in physeal cartilage (Wang, et al). Fulvic acid present in drinking water damages cartilage cells (Yao, et al). Selenium supplementation in selenium deficient areas has been shown to prevent this disease (Yao, et al). However, selenium supplementation in some areas showed no significant effect, proving that deficiency of selenium may not be the dominant cause in KBD (Yao, et al).
of China
. It has also been reported in Siberia
and North Korea
, but incidence in these regions is reported to have decreased with socio-economic development. In China
, KBD is estimated to affect some 2 to 3 million people across China, and 30 million are living in endemic areas. Life expectancy
in KBD regions has been reported to be significantly decreased in relation to selenium deficiency and Keshan disease
(endemic juvenile dilative cardiomyopathia).
The prevalence of KBD in Tibet
varies strongly according to valleys and villages.
Prevalence of clinical symptoms suggestive of KBD reaches 100% in 5-15 year-old children in at least one village. Prevalence rates of over 50% are not uncommon. A clinical prevalence survey carried out in Lhasa prefecture yielded a figure of 11.4% for a study population of approximately 50,000 inhabitants. As in other regions of China, farmers are by far the most affected population group.
The aetiology of KBD remains controversial. Studies of the pathogenesis and risk factors
of KBD have proposed selenium deficiency, inorganic (manganese, phosphate...) and organic matter (humic acids and fulvic acids) in drinking water, fungi on self-produced storage grain (Alternaria
sp., Fusarium
sp.), producing trichotecene (T2) mycotoxins.
Nowadays, most authors accept that the aetiology of KBD is multifactorial, selenium deficiency being the underlying factor that predisposes the target cells (chondrocytes) to oxidative stress
from free-radical
carriers such as mycotoxins in storage grain and fulvic acid in drinking water.
In Tibet, epidemiological studies carried out in 1995-1996 by MSF and coll. showed that KBD was associated with iodine deficiency
and with fungal contamination of barley grains by Alternaria sp., Trichotecium sp., Cladosporium
sp. and Drechslera
sp (Chasseur et al., 1997). Indications existed as well with respect to the role of organic matters in drinking water.
A severe selenium deficiency was documented as well, but selenium status was not associated with the disease, suggesting that selenium deficiency alone could not explain the occurrence of KBD in the villages under study (Moreno-Reyes et al., 1998)
- Belgium started a physical therapy programme aiming at alleviating the symptoms of KBD patients with advanced joint impairment and pain (mainly adults), in Nyemo county, Lhasa prefecture. Physical therapy had significant effects on joint mobility and joint pain in KBD patients. Later on (1994 - 1996), the programme has been extended to several other counties and prefectures in Tibet.
Selenium supplementation, with or without additional antioxidant therapy (Vitamin E
and Vitamin C
) has been reported to be successful, but in other studies no significant decrease could be shown compared to a control group. Major drawbacks of selenium supplementation are logistic difficulties (daily or weekly intake, drug supply), potential toxicity (in case of less controlled supplementation strategies), associated iodine deficiency (that should be corrected before selenium supplementation in order to prevent further deterioration of thyroid status) and low compliance. The latter was certainly the case in Tibet, where a selenium supplementation has been implemented from 1987 to 1994 in areas of high endemicity.
With the mycotoxin theory in mind, backing of grains before storage was proposed in Guanxi province, but results are not reported in international literature. Changing from grain source has been reported to be effective in Heilongjang province and North-Korea.
With respect to the role of drinking water, changing of water sources to deep well water has been reported to decrease the X-ray
metaphyseal detection rate in different settings.
In general, the effect of preventive measures however remains controversial, due to methodological problems (no randomised controlled trials), lack of documentation or, as discussed above, due to inconsistency of results.
Osteochondropathy
Osteochondropathy refers to a disease of the bone and cartilage.However, it is more common to refer to these conditions as one of the following:* chondropathy...
(disease of the bone), which is mainly distributed from northeastern to southwestern China involving 15 provinces (Yao, Pei and Kang, 2011, p.1095-1100). Tibet currently has the highest incidence rate of KBD in China (Yao, et al). Southeast Siberia and North Korea are also other affected areas (Yao, et al). KBD usually involves children aged 5-15, and to date more than a million individuals have suffered from KBD (Wang, Fu, Shi, and Wang, 2011, p. 502-507). The symptoms of KBD include joint pain, morning stiffness in the joints, disturbances of flexion and extension in the elbows, enlarged inter-phalangeal joints and limited motion in many joints of the body (Cao, Li, Shi, Yue, Sun, Chen, Fu, Hughes and Caterson, 2008, p.680-688). Death of cartilage cells in the growth plate and articular surface is the basic pathologic feature; this can result in growth retardation and secondary osteoarthrosis (Yao, et al). Histological diagnosis of KBD is particularly difficult, clinical and radiological examinations have proved to be the best means for identifying KBD (Xiong, 2001, p.147-150). Little is known about the early stages of KBD before the visible appearance of the disease becomes evident in the destruction of the joints (Xiong, 2001, p.147-150).
This disease has been recognized for over 150 years but its etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
has not yet been completely defined (Yao, et al.) Currently the accepted potential causes of KBD include mycotoxins present in grain, trace mineral deficiency in nutrition and high levels of fulvic acid in drinking water (Yao, et al). Selenium and iodine have been considered the most important deficiencies associated with KBD (Yao, et al). Mycotoxins produced by fungi can contaminate grain which may cause KBD because mycotoxins cause the production of free radicals (Yao, et al). T-2 is the mycotoxin implicated with KBD, produced by members of several fungal genera (Wang, et al). T-2 toxin can cause lesions in hematopoietic, lymphoid
Lymphoid
Lymphoid is a term used to describe lymph or the lymphatic system.In the context of lymphoid leukemia, it refers specifically to lymphocytes Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and...
, gastrointestinal, and cartilage tissues, especially in physeal cartilage (Wang, et al). Fulvic acid present in drinking water damages cartilage cells (Yao, et al). Selenium supplementation in selenium deficient areas has been shown to prevent this disease (Yao, et al). However, selenium supplementation in some areas showed no significant effect, proving that deficiency of selenium may not be the dominant cause in KBD (Yao, et al).
Distribution of Kashin-Beck Disease
Kashin-Beck disease occurrence is limited to 13 provinces and 2 autonomous regionsAutonomous area
An autonomous area or autonomous entity is an area of a country that has a degree of autonomy, or freedom from an external authority. Typically it is either geographically distinct from the rest of the country or populated by a national minority. Countries that include autonomous areas are often...
of China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
. It has also been reported in Siberia
Siberia
Siberia is an extensive region constituting almost all of Northern Asia. Comprising the central and eastern portion of the Russian Federation, it was part of the Soviet Union from its beginning, as its predecessor states, the Tsardom of Russia and the Russian Empire, conquered it during the 16th...
and North Korea
North Korea
The Democratic People’s Republic of Korea , , is a country in East Asia, occupying the northern half of the Korean Peninsula. Its capital and largest city is Pyongyang. The Korean Demilitarized Zone serves as the buffer zone between North Korea and South Korea...
, but incidence in these regions is reported to have decreased with socio-economic development. In China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
, KBD is estimated to affect some 2 to 3 million people across China, and 30 million are living in endemic areas. Life expectancy
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...
in KBD regions has been reported to be significantly decreased in relation to selenium deficiency and Keshan disease
Keshan disease
Keshan disease is a congestive cardiomyopathy caused by a combination of dietary deficiency of selenium and the presence of a mutated strain of Coxsackievirus, named after Keshan County of Heilongjiang province, Northeast China, where symptoms were first noted. These symptoms were later found...
(endemic juvenile dilative cardiomyopathia).
The prevalence of KBD in Tibet
Tibet
Tibet is a plateau region in Asia, north-east of the Himalayas. It is the traditional homeland of the Tibetan people as well as some other ethnic groups such as Monpas, Qiang, and Lhobas, and is now also inhabited by considerable numbers of Han and Hui people...
varies strongly according to valleys and villages.
Prevalence of clinical symptoms suggestive of KBD reaches 100% in 5-15 year-old children in at least one village. Prevalence rates of over 50% are not uncommon. A clinical prevalence survey carried out in Lhasa prefecture yielded a figure of 11.4% for a study population of approximately 50,000 inhabitants. As in other regions of China, farmers are by far the most affected population group.
Aetiology and risk factors
Risk factors
A risk factor is a concept in finance theory such as the CAPM, APT and other theories that use pricing kernels. In these models, the rate of return of an asset is a random variable whose realization in any time period is a linear combination of other random variables plus a disturbance term or...
of KBD have proposed selenium deficiency, inorganic (manganese, phosphate...) and organic matter (humic acids and fulvic acids) in drinking water, fungi on self-produced storage grain (Alternaria
Alternaria
Alternaria is a genus of ascomycete fungi. Alternaria species are known as major plant pathogens. They are also common allergens in humans, growing indoors and causing hay fever or hypersensitivity reactions that sometimes lead to asthma...
sp., Fusarium
Fusarium
Fusarium is a large genus of filamentous fungi widely distributed in soil and in association with plants. Most species are harmless saprobes, and are relatively abundant members of the soil microbial community. Some species produce mycotoxins in cereal crops that can affect human and animal health...
sp.), producing trichotecene (T2) mycotoxins.
Nowadays, most authors accept that the aetiology of KBD is multifactorial, selenium deficiency being the underlying factor that predisposes the target cells (chondrocytes) to oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
from free-radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
carriers such as mycotoxins in storage grain and fulvic acid in drinking water.
In Tibet, epidemiological studies carried out in 1995-1996 by MSF and coll. showed that KBD was associated with iodine deficiency
Iodine deficiency in China
Iodine deficiency is still a widespread problem in western, southern and eastern parts of China, as their iodized salt intake level is much lower than the average national level....
and with fungal contamination of barley grains by Alternaria sp., Trichotecium sp., Cladosporium
Cladosporium
Cladosporium is a genus of fungi including some of the most common indoor and outdoor molds. Species produce olive-green to brown or black colonies, and have dark-pigmented conidia that are formed in simple or branching chains....
sp. and Drechslera
Drechslera
Drechslera is a genus of fungi. Many of the species in this genus are plant pathogens. Drechslera puttaparthii is a new species found recently by Dr.Vijay Kumar. at Department of Biosciences. Sri Sathya Sai institute of higher learning. Prasanthinilayam....
sp (Chasseur et al., 1997). Indications existed as well with respect to the role of organic matters in drinking water.
A severe selenium deficiency was documented as well, but selenium status was not associated with the disease, suggesting that selenium deficiency alone could not explain the occurrence of KBD in the villages under study (Moreno-Reyes et al., 1998)
Treatment
Treatment of KBD is so far palliative. Surgical corrections have been made with success by Chinese and Russian orthopaedists. By the end of 1992, Médecins Sans FrontièresMédecins Sans Frontières
' , or Doctors Without Borders, is a secular humanitarian-aid non-governmental organization best known for its projects in war-torn regions and developing countries facing endemic diseases. Its headquarters are in Geneva, Switzerland...
- Belgium started a physical therapy programme aiming at alleviating the symptoms of KBD patients with advanced joint impairment and pain (mainly adults), in Nyemo county, Lhasa prefecture. Physical therapy had significant effects on joint mobility and joint pain in KBD patients. Later on (1994 - 1996), the programme has been extended to several other counties and prefectures in Tibet.
Prevention of Kashin-Beck Disease
Prevention of Kashin-Beck Disease has a long history. Intervention strategies were mostly based on one of the three major etiologic theories.Selenium supplementation, with or without additional antioxidant therapy (Vitamin E
Tocopherol
Tocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...
and Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
) has been reported to be successful, but in other studies no significant decrease could be shown compared to a control group. Major drawbacks of selenium supplementation are logistic difficulties (daily or weekly intake, drug supply), potential toxicity (in case of less controlled supplementation strategies), associated iodine deficiency (that should be corrected before selenium supplementation in order to prevent further deterioration of thyroid status) and low compliance. The latter was certainly the case in Tibet, where a selenium supplementation has been implemented from 1987 to 1994 in areas of high endemicity.
With the mycotoxin theory in mind, backing of grains before storage was proposed in Guanxi province, but results are not reported in international literature. Changing from grain source has been reported to be effective in Heilongjang province and North-Korea.
With respect to the role of drinking water, changing of water sources to deep well water has been reported to decrease the X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
metaphyseal detection rate in different settings.
In general, the effect of preventive measures however remains controversial, due to methodological problems (no randomised controlled trials), lack of documentation or, as discussed above, due to inconsistency of results.