title: Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats.
abstract: Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.
authors: Charles River Laboratories, 22022 Transcanadienne, Senneville, Montréal, Québec, Canada H9X 3R3.
authors: Rana
authors: R
authors: Samadfam
authors: Malaika
authors: M
authors: Awori
authors: Agnes
authors: A
authors: Bénardeau
authors: Frieder
authors: F
authors: Bauss
authors: Elena
authors: E
authors: Sebokova
authors: Matthew
authors: M
authors: Wright
authors: Susan Y
authors: SY
authors: Smith
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001862:Bone Resorption / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010455:Peptides / Q000097:blood; D000077205:Pioglitazone; D011897:Random Allocation; D051381:Rats; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D010455:Peptides; D045162:Thiazolidinediones; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D011345:Fenofibrate; D000077205:Pioglitazone