Osteoporosis Associated With Pulmonary Silicosis in an Equine Bone Fragility Syndrome

Abstract

California horses incur a bone fragility syndrome manifested by pathologic fractures. This study investigated gross, radiographic, and histologic features of the disorder as well as relationships with silicosis and levels of heavy metals and trace minerals through a postmortem study of 9 affected and 3 unaffected horses. Bones and soft tissues were evaluated grossly and histologically. Bones, lymph nodes, and lung tissue were evaluated radiographically. Tissues were evaluated for silicon levels, intracytoplasmic crystals, heavy metals, and trace minerals. All 9 affected horses had osteoporosis and clinical or subclinical pulmonary disease due to silicosis (8/9) or pneumoconiosis (1/9). All affected horses had radiographic findings consistent with osteopenia and histologic evidence of osteoporosis characterized by osteopenia, numerous resorption cavities, cement lines, and a mosaic lamellar pattern indicative of multiple remodeling events. Silicosis was characterized by widespread pulmonary granuloma formation with fibrosis; variable tracheobronchiolar and mediastinal granulomatous lymphadenitis; intracellular crystals within lung and lymph node macrophages; and pronounced lymph node fibrosis, focal necrosis, and dystrophic calcification. Crystals in lung (6/9) and lymph node (8/9) tissues were identified as cytotoxic silica dioxide polymorphs. Lung and liver tissue from affected horses had elevated levels of elemental silicon. Osteoporosis was highly correlated (r = 0.8, P < .01) with silicosis. No abnormalities in heavy metal or trace minerals were detected. This evaluation indicated that horses with bone fragility disorder have systemic osteoporosis associated with fibrosing pulmonary silicosis. The etiopathogenesis of the bone fragility syndrome is unknown; however, this study provides circumstantial evidence for a silicate associated osteoporosis.

Evaluation of bone mineral density and 25-hydroxyvitamin D levels in subjects with silica exposure

“…Moreover, osteoporosis has been reported in silicotic horses, rodent models, and in a young man with silicosis, although the exact relationship and underlying mechanism are not clear yet [7][8][9]. It has been shown that pro-inflammatory cytokines such as IL-1, IL-6, TNF-a and soluble receptor activators for nuclear factor-K B ligand (RANKL) have been released due to the inflammatory cascades in patients with silicosis [10,11].…”

Use of zoledronate for treatment of a bone fragility disorder in horses

“…These include exposure to high concentrations of the cristobalite form of silicate in the Monterey Formation region of California, causing chronic systemic inflammation; direct dissemination of silicate-laden macrophages to bone marrow secondary to pulmonary silicosis; and abnormal osteoclastmediated resorption and remodeling of bone similar to Paget' s disease of bone in humans. [1][2][3][4] Other causes of pathological bone resorption include chronic corticosteroid use, primary or secondary hyperparathyroidism, and calcium or vitamin D deficiencies 11 ; however, prolonged corticosteroid use has not been a historical finding in horses in which this BFD is diagnosed, and no consistent abnormalities in circulating concentrations of parathyroid hormone, calcium, or other standard biochemical variables have been identified in previous studies 1-4 of horses with this disorder.…”

“…[1][2][3][4] Pulmonary silicosis in horses has been attributed to the inhalation of the fibrogenic and cytotoxic cristobalite form of silicate, and cristobalite is considered to be a candidate for the etiologic agent directly responsible for this BFD. 4 Alternatively, exposure to cristobalite may initiate a sequence of events that eventually results in the condition; a recent study 4 of 9 horses with this BFD that underwent necropsy examination identified histopathologic evidence of osteoporosis and abnormal osteoclast-mediated bone resorption. 4 Treatment targeting abnormal osteoclast activity …”

“…4 Alternatively, exposure to cristobalite may initiate a sequence of events that eventually results in the condition; a recent study 4 of 9 horses with this BFD that underwent necropsy examination identified histopathologic evidence of osteoporosis and abnormal osteoclast-mediated bone resorption. 4 Treatment targeting abnormal osteoclast activity …”

Multifocal discrete osteolysis in a horse with silicate associated osteoporosis

“…cristobalite) (Arens et al . ). Granulomas featuring necrosis and fibrosis within the lungs and draining lymph nodes characterise the lesions induced by cristobalite in horses (Schwartz et al .…”