Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

• Published in: Journal of endocrinology Vol. 212; no. 2; pp. 179 - 186
• Main Authors: Samadfam, Rana, Awori, Malaika, Bénardeau, Agnes, Bauss, Frieder, Sebokova, Elena, Wright, Matthew, Smith, Susan Y
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.02.2012
• Subjects: Adiposity - drug effects; Animals; Biological and medical sciences; Biomarkers - blood; Body composition; Bone (trabecular); Bone and Bones - chemistry; Bone and Bones - drug effects; Bone composition; Bone Density - drug effects; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - therapeutic use; Bone loss; Bone mass; Bone mineral content; Bone mineral density; Bone Resorption - chemically induced; Bone Resorption - etiology; Bone Resorption - prevention & control; Collagen Type I - blood; Data processing; Diseases of the osteoarticular system; Drug Therapy, Combination; Female; Femur; Fenofibrate; Fenofibrate - administration & dosage; Fenofibrate - therapeutic use; Fractures; Fundamental and applied biological sciences. Psychology; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - adverse effects; Hypolipidemic Agents - therapeutic use; Lipids; Medical sciences; Menopause; Metaphysis; Osteocalcin - blood; Osteoporosis, Postmenopausal - blood; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - physiopathology; Osteoporosis. Osteomalacia. Paget disease; Ovariectomy; Peptides - blood; Peroxisome proliferator-activated receptors; pioglitazone; PPAR alpha - agonists; PPAR gamma - agonists; Random Allocation; Rats; Regular papers; Risk assessment; Spine (lumbar); Thiazolidinediones - administration & dosage; Thiazolidinediones - adverse effects; Thiazolidinediones - therapeutic use; Vertebrates: endocrinology; Agonist; Ovariectomy; Rat; Fibrate derivatives; Pioglitazone; Diseases of the osteoarticular system; Rodentia; Thiazolidinedione derivatives; PPAR-γ receptor; Fenofibrate; Vertebrata; Mammalia; Treatment; Animal; Acceleration; Osteopenia
• DOI: 10.1530/JOE-11-0356
• ISSN: 0022-0795

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.