Article thumbnail

The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats

By Astrid K Stunes, Irene Westbroek, Björn I Gustafsson, Reidar Fossmark, Jan H Waarsing, Erik F Eriksen, Christiane Petzold, Janne E Reseland and Unni Syversen
Topics: Research Article
Publisher: BioMed Central
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1999). A: Centrifugal isolation of bone marrow from bone: an improved method for the recovery and quantitation of bone marrow osteoprogenitor cells from rat tibiae and femurae. Calcif Tissue Int
  2. (2003). Abu-Amer Y: Activation of peroxisome proliferator-activated receptor-gamma inhibits differentiation of preosteoblasts.
  3. (1990). Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature
  4. (2007). Chong LW, Evans RM: PPAR-gamma regulates osteoclastogenesis in mice. Nat Med
  5. (2003). CS: Activation of peroxisome proliferator-activated receptor-gamma inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts.
  6. (1996). DC: Peroxisome proliferator-activated receptorgamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. Mol Pharmacol
  7. (2002). DE: The mechanisms of action of PPARs. Annu Rev Med
  8. (2006). Delmas PD: Bone quality–the material and structural basis of bone strength and fragility.
  9. (2000). Demer LL: Peroxisome proliferator-activated receptor activators modulate the osteoblastic maturation of MC3T3-E1 preosteoblasts.
  10. (2007). Deng HW: Correlation of Obesity and Osteoporosis - Effect of Fat Mass on the Determination of Osteoporosis.
  11. (2006). Diabetes, TZDs, and Bone: A Review of the Clinical Evidence. PPAR Res
  12. (2005). Distinct effects of PPARgamma insufficiency on bone marrow cells, osteoblasts, and osteoclastic cells. J Bone Miner Metab
  13. (2001). Drevon CA: Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res
  14. (2004). DT: Reduced serum dipeptidyl peptidaseIV after metformin and pioglitazone treatments.
  15. (1994). Ekeland A: Muscle contraction increases the in vivo structural strength to the same degree in osteopenic and normal rat tibiae.
  16. (2004). Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int
  17. (2006). et al: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.
  18. (2004). et al: PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors.
  19. (2006). et al: Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.
  20. (2008). Fruhbeck G: The bone-adipose axis in obesity and weight loss. Obes Surg
  21. (2008). GJ: Pioglitazone and dexamethasone induce adipogenesis in D1 bone marrow stromal cell line, but not through the peroxisome proliferator-activated receptor-gamma pathway. Life Sci
  22. (2007). Gluszko P: Effects of hypolipemic drugs on the osteoprotegerin - sRANKL system in patients with coronary artery disease. Thromb Haemost
  23. (1993). Gundersen HJ: Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions.
  24. (2006). Gustafsson BI: Long-term fluoxetine administration does not result in major changes in bone architecture and strength in growing rats.
  25. (1997). Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferatoractivated receptors alpha and delta. Proc Natl Acad Sci USA
  26. (2002). I: Microarray Analysis of Gene Expression Changes in Mouse Liver Induced by Peroxisome Proliferator- Activated Receptor [alpha] Agonists. Biochem Biophys Res Commun
  27. (2005). Inhibition of NF-kappaB signaling by fenofibrate, a peroxisome proliferator-activated receptor-alpha ligand, presents a therapeutic strategy for rheumatoid arthritis. Clin Exp Rheumatol
  28. (2006). Intracellular signalling pathways activated by leptin.
  29. (2007). IR: The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial.
  30. (2004). Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome. Int J Obes Relat Metab Disord
  31. (2007). JA: PPAR agonists modulate human osteoclast formation and activity in vitro. Bone
  32. (2008). JE: The PPARgamma-selective ligand BRL-49653 differentially regulates the fate choices of rat calvaria versus rat bone marrow stromal cell populations.
  33. (2002). Jilka RL: Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology
  34. (1999). Jilka RL: Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2.
  35. (2005). Jilka RL: Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology
  36. (2002). JL: A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. Diabetes Care
  37. (2001). JW: IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor gamma 1. Proc Natl Acad Sci USA
  38. (2004). Karaplis AC: Rosiglitazone impacts negatively on bone by promoting osteoblast/ osteocyte apoptosis.
  39. (2004). Lecka-Czernik B: Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology
  40. (2007). Lecka-Czernik B: Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology
  41. (2005). Long-term prediction of three-dimensional bone architecture in simulations of pre-, peri- and post-menopausal microstructural bone remodeling. Osteoporos Int
  42. (2000). Marshak DR: Activation of peroxisome proliferator-activated receptor-gamma pathway inhibits osteoclast differentiation.
  43. (2005). Meinke PT: PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci
  44. (2003). Mineralizing fibroblast-colony-forming assays. Methods Mol Med
  45. (2008). Miyahara T: Activation of peroxisome proliferator-activated receptor gamma inhibits TNF-alpha-mediated osteoclast differentiation in human peripheral monocytes in part via suppression of monocyte chemoattractant protein-1 expression. Bone
  46. (2007). O’Connell MB: Evolution of peroxisome proliferator-activated receptor agonists. Ann Pharmacother
  47. (2006). O’Rahilly S, et al: International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev
  48. (1996). Olefsky JM: Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes
  49. (2005). PD: In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography.
  50. (2008). PV: Utility of the ovariectomized rat as a model for human osteoporosis in drug discovery. Methods Mol Biol
  51. (1997). Quantification of Bone Microarchitecture with the Structure Model Index. Comput Methods Biomech Biomed Engin
  52. (1987). Reddy JK: Peroxisome proliferation and hepatocarcinogenesis. Carcinogenesis
  53. (2007). Relationships between fat and bone. Osteoporos Int
  54. (2004). Reseland JE: Adiponectin and its receptors are expressed in bone-forming cells.
  55. (2009). Reseland JE: Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord
  56. (2002). Reseland JE: Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: Impact on differentiation markers, apoptosis, and osteoclastic signaling.
  57. (2004). Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes Res
  58. (2010). Rosiglitazone: what went wrong? BMJ
  59. (2007). Rothenbacher D: The effect of thiazolidinediones on adiponectin serum level: a meta-analysis. Diabetes Obes Metab
  60. (2007). Shamiss A: Effect of PPAR-gamma agonist on adiponectin levels in the metabolic syndrome: lessons from the high fructose fed rat model.
  61. (2006). Short-term pioglitazone treatment prevents free fatty acid-induced hepatic insulin resistance in normal rats: possible role of the resistin and adiponectin. Biochem Biophys Res Commun
  62. (2005). SJ: A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care
  63. (2007). SK: Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care
  64. (2008). Skeletal consequences of thiazolidinedione therapy. Osteoporos Int
  65. (2006). TA: Surface-specific effects of a PPARgamma agonist, darglitazone, on bone in mice. Bone
  66. (1999). Takeuchi Y: Thiazolidinediones inhibit osteoclast-like cell formation and bone resorption in vitro. Endocrinology
  67. (2001). Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.
  68. (2004). The many lives of leptin. Peptides
  69. (2008). The Peroxisome Proliferator Activator Receptor Alpha/Delta Agonists Linoleic Acid and Bezafibrate Upregulate Osteoblast Differentiation and Induce Periosteal Bone Formation In Vivo. Calcif Tissue Int
  70. (2007). Theocharis S: Peroxisome proliferatoractivated receptors (PPARs) in the control of bone metabolism. Fundam Clin Pharmacol
  71. (2006). Thiazolidinedione use and bone loss in older diabetic adults.
  72. (2003). Thommesen L: PPAR-Alpha Agonists Increase Bone Mineral Density in Female Rats.
  73. (2008). TL: Pathogenesis of age-related osteoporosis: impaired mechanoresponsiveness of bone is not the culprit. PLoS One
  74. (1996). Wahli W: PPAR tissue distribution and interactions with other hormone-signaling pathways.
  75. (2005). Zarzuelo A: A diet supplemented with husks of Plantago ovata reduces the development of endothelial dysfunction, hypertension, and obesity by affecting adiponectin and TNF-alpha in obese Zucker rats.