Matthew G. Durham
Silicosis and Osteoporosis Syndrome
Inhalation of silicates causes pneumoconiosis in humans, horses, dogs, and other species. In humans, silicate pneumoconiosis is an important occupational disease in industries in which silicate crystals (typically quartz) are fractured into microcrystalline forms. In horses, pneumoconiosis is recognized in geographic areas with soils that contain cristobalite, an uncommon silicate crystal formed through volcanic action or through compression of diatomaceous deposits. Outbreaks can be seen when this powdery rock type is exposed by disturbance of soil during construction.
A bone disease characterized by progressive osteoporosis and skeletal deformation is also commonly seen in horses from regions where silicosis is seen. Respiratory tract and skeletal manifestations are often both found to various degrees in the same horse. On farms where the condition is endemic, some horses have predominantly respiratory signs, whereas others have predominantly skeletal signs.
Etiopathogenesis
Pneumoconiosis
After gaining entrance into the alveolus, particles of crystalline silicates in the form of Sio2 smaller than about 5 µm are phagocytosed by alveolar macrophages. These reactive silicate particles are cytotoxic and fibrogenic, inducing a persistent granulomatous process that leads to fibrosis. An acute severe form in humans, characterized by eosinophilic infiltration, has not been reported in horses. Length and dose of exposure, as well as factors specific to each individual’s immune response, likely influence the severity and progression of clinical signs.
Osteoporosis
The most likely cause of bone fragility in affected horses appears to be increased osteoclastic and possible collagenolytic activity in response to chronic inflammation. Inhaled silicates are known to cause osteoporosis in rodents, presumably through persistent macrophage stimulation. This disease can be considered a silicate-associated osteoporosis (SAO), although a direct cause-and-effect relationship has not been established between pneumoconiosis and bone fragility.
No consistent abnormalities in calcium or phosphate concentrations or in other routine serum biochemical tests are seen, making true metabolic bone disease unlikely. Although parathyroid hormone levels are higher than normal, this disease does not share most characteristics with equine hyperparathyroidism. It is likely that bone turnover induces secondary hyperparathyroidism.
Although high phosphate concentrations are found in diatomaceous soils, serum concentrations normalize when dietary levels normalize. High dietary phosphate would not explain bone remodeling that persists in affected horses that have been removed from endemic areas for years. Systemic corticosteroids can contribute to osteoporosis, but most affected horses do not have a history of corticosteroid treatment.
Silicate crystals appear to be the most likely etiologic candidate given the common geographic distribution of pneumoconiosis and SAO, particularly with outbreaks of both forms arising on facilities where soil excavations have occurred. Although many horses with signs of SAO have no respiratory signs, chronic mild pneumoconiosis is often clinically silent, and pulmonary changes are seen only radiographically or histologically.
Silicates are crystals composed of silicon and other elements, with a molecular configuration of repeating units extending in all three dimensions. Silicon dioxide is by far the most abundant crystal in the earth’s crust, existing primarily in the form of quartz. Cristobalite, a much less common silicate, is also composed of silicon dioxide, but has a crystalline structure different from that of quartz.
All common crystalline forms of silicon dioxide can cause pneumoconiosis when inhaled into the alveoli. However, quartz tends to exist naturally in stable large crystals that do not reach the respiratory tract down to the level of the alveoli. Only through mechanical pulverization, as occurs in certain industrial occupations, can the crystal gain access to the lower airway. Cristobalite is a less stable crystalline structure in its pure form, making it naturally more powdery and easily inhaled into the lower airways.
Silicon is essential for normal osteoblast function and collagen production, although the direct mechanisms are incompletely understood. Although known mild toxic effects of orally ingested silicates are recognized, there is a dose-related toxicosis seen from inhaled silicates. In humans with osteoporosis, dietary silicon can enhance bone production. Ingested silicon is thought to be absorbed mainly as orthosilicic acid, which is found in many liquids or created in the acidic environment of the stomach from crystalline forms. For this reason, it appears unlikely that ingestion of cristobalite by horses would introduce intact crystalline silicates to the system, and systemic levels of amorphous silica should stabilize quickly when the horse is removed from a bioavailable rich source. Whether the presence of high levels of sequestered cristobalite in the lungs or lymph nodes has an effect on systemic silicic acid levels is unknown.
In humans, silicosis has not been associated directly with an increased incidence of osteoporosis. However, humans with silicosis have an increased incidence of autoimmune diseases such as systemic lupus erythematosus, scleroderma, and rheumatoid arthritis, all of which carry an increased incidence of concurrent osteoporosis.
Many of the clinical manifestations of SAO in horses have similar features to autoimmune disease. The cervical vertebral osteoporosis and arthritis seen in horses with SAO have similarities to the cervical arthritic changes that develop in many humans with rheumatoid arthritis, but the scapular displacement and lordosis that develop in horses cannot be entirely explained by osteoporosis alone. Ligamentous laxity in the cervical spine in humans with rheumatoid arthritis can lead to cervical vertebral luxations. Stimulation of proteolytic enzymes is known to contribute both to arthritis and to osteoporosis in human patients. Increased levels of collagen breakdown products are present in humans with osteoporosis.
Paget’s disease in humans shares many characteristics with SAO, including skeletal deformations, pathologic fractures, and lytic bone lesions.
Geographic Distribution
The full extent of geographic distribution of SAO horses is not fully understood. Cases have been seen in several counties in the coastal ranges of California, with Monterey County being the historical epicenter. Cases have also been seen in San Luis Obispo, Santa Cruz, Napa, and Sonoma counties. However, similar geologic formations are present throughout the world, making it unclear why this disease has not been recognized elsewhere.
The geographic Monterey Formation extends from Point Reyes (north of San Francisco) through the coastal ranges, in outcroppings reaching as far south as Baja California in Mexico. The Formation consists largely of transformed diatomaceous deposits that contain high levels of cristobalite. Napa and Sonoma counties have cristobalite deposits that are largely volcanic in origin. Areas with diatomaceous deposits are also present throughout this area.
It seems likely that there are other sources of cristobalite or other silicate forms dispersed throughout the world where diatomaceous deposits or certain types of volcanic activity have occurred. Although cristobalite is well established as a causative agent of pneumoconiosis in horses, the possibility of a coexisting factor in these geographic regions has not been eliminated as a potential cause of SAO.
