title: Vitamin D supplementation protects against bone loss following inhalant organic dust and lipopolysaccharide exposures in mice.
abstract: Systemic bone loss is associated with airway inflammatory diseases; yet, strategies to halt disease progression from inhalant exposures are not clear. Vitamin D might be a potentially protective approach against noxious respirable environmental exposures. We sought to determine whether vitamin D supplementation represents a viable lung- and bone-protective strategy following repetitive inhalant treatments with organic dust extract (ODE) or lipopolysaccharide (LPS) in mice. C57BL/5 mice were maintained on diets with low (1 IU/D/g) or high (10 IU/D/g) vitamin D for 5 weeks and treated with ODE from swine confinement facilities, LPS, or saline daily for 3 weeks per established intranasal inhalation protocol. Lungs, hind limbs, and sera were harvested for experimental outcomes. Serum 25-hydroxyvitamin D levels were tenfold different between low and high vitamin D treatment groups with no differences between inhalant agents and saline treatments. Serum calcium levels were not affected. There was no difference in the magnitude of ODE- or LPS-induced inflammatory cell influx or lung histopathology between high and low vitamin D treatment groups. However, high vitamin D treatment reversed the loss of bone mineral density, bone volume, and bone micro-architecture deterioration induced by ODE or LPS as determined by micro-CT analysis. Bone-resorbing osteoclasts were also reduced by high vitamin D treatment. In the low vitamin D treatment groups, ODE induced the greatest degree of airway inflammatory consequences, and LPS induced the greatest degree of bone loss. Collectively, high-concentration vitamin D was protective against systemic bone loss, but not airway inflammation, resulting from ODE- or LPS-induced airway injury.
authors.affiliation: Rheumatology Division, Department of Internal Medicine, University of Nebraska Medical Center, 986350 Nebraska Medical Center, Omaha, NE, 68198-6350, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Dusad
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Thiele
authors.forename: Lynell W
authors.initials: LW
authors.lastname: Klassen
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duryee
authors.forename: Ted R
authors.initials: TR
authors.lastname: Mikuls
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Staab
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
authors.forename: William W
authors.initials: WW
authors.lastname: West
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Romberger
authors.forename: Jill A
authors.initials: JA
authors.lastname: Poole
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002118:Calcium / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements; D004391:Dust; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D006799:Housing, Animal; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011859:Radiography; D013552:Swine; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D004391:Dust; D008070:Lipopolysaccharides; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium