Musculoskeletal system

Xenobiotic exposure can adversely affect bones, joints, connective tissue, and muscles. Rheumatoid arthritis (RA), osteoporosis, osteomalacia, systemic sclerosis (SS), scleroderma (SSc), SLE, and spina bifida are musculoskeletal diseases that have been associated with toxic chemical exposures. Most of these associations, however, have been made to single chemical exposures and not mixtures. This chapter will cite the evidence on which those associations are based and discuss the available examples of mixtures that have been implicated. 

Chemicals that are toxic to the musculoskeletal system are listed in Table 28.1 [1-7]. 

Human Tuaicolagy of Chemical Mixtures. DOI 10.101(VB978-l-4377-3463.8.0002. X 2011 Elsevier Inc. All rights reserved 

SSc is a chronic autoimmune disease characterized by excessive deposition of collagen and fibrosis (formation of scar tissue) in the skin and other body organs. Though the local manifestation of this disease is not serious, SS, the serious manifestation, can be fatal. Since exposures to the same chemicals have been associated with both variants of this disease, they will be discussed together. 

Occupations that are associated with SSc and SS include those where exposures to organic solvents and silica are common [1, 11-14]. A partial list of these occupations is given in Table 28.2 [1, 11-14], and a list of the chemicals which have been associated with SSc and SS is given in Table 28.3 [1,9,13-19]. 

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Drugs Used to Treat Disorders of the Musculoskeletal System... 

Arthritis is the inflammation of a joint. The term is frequently used to refer to any disease involving pain or stiffness of the musculoskeletal system. 

Routine gross and histopathological examinations revealed no treatment-related effects on the musculoskeletal system of dogs exposed to 0.03, 0.1, or 0.3 mg/kg/day methyl parathion in the diet for 1 year (Suba 1981). Chronic dietary exposure to methyl parathion did not induce musculoskeletal effects in mice fed 16.2 mg/kg/day or rats fed 2 mg/kg/day (NCI 1979). 

Musculoskeletal Effects. Very limited data were available regarding the effects of endosulfan on the musculoskeletal system. However, the available animal data did not indicate that this system is adversely affected following either inhalation or oral exposure to endosulfan (FMC 1965, 1967 Hoechst 1984b, 1984c, 1988b, 1989a, 1989c). Thus, persons exposed to endosulfan would not be expected to experience adverse effects on the musculoskeletal system. 

The musculoskeletal system consists of bones, blood vessels, nerves, ligaments, tendons, muscles, and cartilage, which work together to perform the structural and kinematic functions of the organism. These musculoskeletal tissues all have a composite structure of cells embedded in a matrix produced by the cells themselves. 

The musculoskeletal system consists of the muscles, bones, joints, tendons, and ligaments. Disorders related to the musculoskeletal system often are classified by etiology. Acute soft-tissue injuries include strains and sprains of muscles and ligaments. Repeated movements in sports, exercise, work, or activities of daily living may lead to repetitive strain injury, where cumulative damage occurs to the muscles, ligaments, or tendons.1-3 While tendonitis and bursitis can arise from acute injury, more commonly these conditions occur as a result of chronic stress.3,4 Other forms of chronic musculoskeletal pain, such as pain from rheumatoid arthritis (see Chap. 54) or osteoarthritis (see Chap. 55), are discussed elsewhere in this text. 

Physical examination of the musculoskeletal system (e.g., biceps, triceps, quadriceps, temporalis, deltoid, and interosseus muscles) for loss of muscle mass, and examination of the skin and mucous membranes for abnormalities (e.g., noting dry or flaky skin, bruising, edema, ascites, poorly healing wounds) and loss of subcutaneous fat... 

Polyalphaolefin Hydraulic Fluids. There is limited information on the potential of polyalphaolefin hydraulic fluids to induce musculoskeletal effects. Kyphosis, a deformity of the spine characterized by extension flexion was observed in rats exposed to 880-5,030 mg/m3 (concentration eliciting response not reported) of a polyalphaolefin hydraulic fluid designated at B85-174 for 4 hours (Kinkead et al. 1987b). It is not known if this effect is related to damage to the musculoskeletal system or to neurological damage. This is the only study that examined musculoskeletal effects. Thus, the likelihood of musculoskeletal effects occurring in humans exposed to polyalphaolefin hydraulic fluids cannot be determined. 

Adverse effects on the respiratory system, cardiovascular system, gastrointestinal tract, blood, musculoskeletal system, liver, or kidneys have not been observed in humans exposed to bromomethane by the dermal route (e.g., Butler et al. 1945 Mine 1969 Wyers 1945 Zwaveling et al. 1987). 

Only one report detailing musculoskeletal effects in animals after oral exposure to chloroform was located. In that study, no histopathological changes were observed in the musculoskeletal system of rats and mice after chronic gavage exposure to 200 and 477 mg/kg/day TWA chloroform in oil, respectively (NCI 1976). 

Musculoskeletal Effects. Little data is available that examines the effects of chloroform toxicity on the musculoskeletal system however, it appears that chloroform has few significant toxic effects on this system. 

Musculoskeletal Effects. There were no reports of human exposure that resulted in musculoskeletal effects. The few reports that examined the musculoskeletal system after exposure to 1,4-dichlorobenzene in laboratory animals failed to elicit detectable changes in this system. 

No histopathological changes were noted in the musculoskeletal system of rats or dogs exposed to up to 100 mg/m deodorized kerosene vapor for 13 weeks (Carpenter et al. 1976). Only one study of this effect was located. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans after inhalation, oral, or dermal exposure to fuel oils. No histopathological changes were noted in the musculoskeletal systems of rats and dogs exposed by inhalation to up to 100 mg/m deodorized kerosene vapor for 13 weeks (Carpenter et al. 1976). Mice treated dermally with marine diesel fuel and JP-5 (up to 500 mg/kg/day) also displayed no detectable adverse effects to the musculoskeletal system (NTP/NIH 1986). The limited information available on animals is not sufficient to assess its relevance to human health. 

It should be noted that in humans opportunities for exposure to acutely lethal doses of chlorodibromomethane are remote. In animals, no direct effects of oral exposure to chlorodibromomethane have been noted for the respiratory, cardiovascular, hematologic, or musculoskeletal systems or on the skin or eyes. One study indicated that short-term oral exposure of mice to doses of 125mg/kg/day could produce significant changes in both the humoral and the cell-mediated immune systems. ... 

As was already mentioned, piroxicam also is a nonsteroidal, anti-inflammatory drug. It is used in inflammatory and degenerative diseases of the musculoskeletal system that are accompanied by painful symptoms. It is used for rheumatic heart disease, nonspecific infectious polyarthritis, gouty arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, arthrosis, back pain, nenralgia, myalgia, and other diseases associated with inflammation. Synonyms for piroxicam are feldene, dexicam, roxenan, and others. 

Musculoskeletal Effects. No treatment-related lesions of the musculoskeletal system were observed in rats exposed to dose levels of 20 mg/kg/day hexachlorobutadiene for up to 148 days (Harleman and Seinen 1979 Schwetz et al. 1977) or 2 years (Kociba et al. 1977a). 

Musculoskeletal Effects. No studies in humans or animals have been conducted to evaluate the effects of carbon tetrachloride on the musculoskeletal system. Accordingly, conclusions cannot be made about such potential effects in humans. 

M Musculoskeletal system 710-739 Diseases of the musculoskeletal system and connective tissue... 

M Musculoskeletal system N Central nervous system R Respiratory system... 

Rheumatic disease is defined as disease of connective tissue and medical disorders of the musculoskeletal system . The medical discipline concerned with these diseases is referred to as rheumatology. The majority of rheumatic diseases are soft tissue rheumatism and nonspecific low back pain (LBP), autoimmune inflammatory rheumatic diseases, osteoarthritis (OA), osteoporosis, crystal-deposition disease and infectious arthritis. 

Chronic tuberculous arthritis is not at all rare in developing countries. Mycobacterial tuberculosis can directly or indirectly affect the musculoskeletal system. Most commonly there is a direct musculoskeletal involvement of M. tuberculosis which may lead to spondylitis, osteomyelitis, septic arthritis and tenosynovitis. M. tuberculosis has become an important pathogen in rheumatic diseases since the use of anti-TNF-a biopharmaceuticals was introduced. 

Adverse effects are usually due to excessive doses (which may occur if the initial increase in metabolism is too rapid) and correspond to symptoms of hyperthyroidism, but they usually disappear after dose reduction or withdrawal of treatment. The most common adverse effects affect the following system as Heart arrhythmias, anginal pain, Central nervous system headache, hyperactivity, sweating, tremor, heat intolerance, Gastrointestinal tract diarrhoea, excessive weight loss, vomiting, Musculoskeletal system muscle cramps, muscle weakness. 

During the perinatal period, there is an absolute requirement for thyroid hormone for the development and maturation of the nervous and musculoskeletal systems. In the perinatal nervous system, thyroid hormone plays a critical role in normal growth of the cerebral and cerebellar cortices, the proliferation of axons, the branching of dendrites, synaptogenesis, myeUnation, cell migration, and so on. 

Musculoskeletal Effects. Histological examination of tissues from the musculoskeletal system of rats and mice exposed to 2,3-benzofuran by gavage for up to 2 years showed a compound-related increase in bone degeneration (fibrous osteodystrophy) in chronically-exposed male rats (NTP 1989). The observed increase in bone degeneration, which was not statistically significant at doses of either 30 or 60 mg/kg/day, was not considered a direct effect of 2,3-benzofuran exposure, but as secondary to calcium and phosphate imbalance due to increased severity of nephropathy in male rats caused by... 

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