Pioglitazone increases bone marrow fat in type 2 diabetes: results from a randomized controlled trial

Grey, Andrew; Beckley, Vaughan; Doyle, Anthony; Fenwick, Sheryl; Horne, Anne; Gamble, Greg; Bolland, Mark J

doi:10.1530/eje-11-1075

Cited by 47 publications

(31 citation statements)

References 19 publications

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“…PPAR␥ agonists have been shown to increase marrow fat and may be associated with decreased bone quality (4,22). We undertook a study to assess qualitative as well as volumetric quantitative changes in marrow fat due to PPAR␥ agonist, and to ask whether PPAR␥-induced marrow fat interfered with exercise-stimulated bone density.…”

Section: Discussionmentioning

confidence: 99%

Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice

et al. 2015

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The contribution of marrow adipose tissue (MAT) to skeletal fragility is poorly understood. Peroxisome proliferator-activated receptor (PPAR)γ agonists, associated with increased fractures in diabetic patients, increase MAT. Here, we asked whether exercise could limit the MAT accrual and increase bone formation in the setting of PPARγ agonist treatment. Eight-week-old female C57BL/6 mice were treated with 20-mg/kg · d rosiglitazone (Rosi) and compared with control (CTL) animals. Exercise groups ran 12 km/d when provided access to running wheels (CTL exercise [CTL-E], Rosi-E). After 6 weeks, femoral MAT (volume of lipid binder osmium) and tibial bone morphology were assessed by microcomputer tomography. Rosi was associated with 40% higher femur MAT volume compared with CTL (P < .0001). Exercise suppressed MAT volume by half in CTL-E mice compared with CTL (P < .01) and 19% in Rosi-E compared with Rosi (P < .0001). Rosi treatment increased fat markers perilipin and fatty acid synthase mRNA by 4-fold (P < .01). Exercise was associated with increased uncoupling protein 1 mRNA expression in both CTL-E and Rosi-E groups (P < .05), suggestive of increased brown fat. Rosi increased cortical porosity (P < .0001) but did not significantly impact trabecular or cortical bone quantity. Importantly, exercise induction of trabecular bone volume was not prevented by Rosi (CTL-E 21% > CTL, P < .05; Rosi-E 26% > Rosi, P < .01). In summary, despite the Rosi induction of MAT extending well into the femoral diaphysis, exercise was able to significantly suppress MAT volume and induce bone formation. Our results suggest that the impact of PPARγ agonists on bone and marrow health can be partially mitigated by exercise.

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Section: Discussionmentioning

confidence: 99%

Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice

et al. 2015

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“…Despite compelling evidence from cell-based models, the impact of marrow adipose tissue on skeletal homeostasis or bone loss disorders is less clear owing to inconsistencies in findings from clinical studies [76, 77]. This challenge to the classical view on the inverse association between adipogenic and osteoblastogenic signaling is further bolstered by reports of a lack of association between marrow adiposity and skeletal phenotypes in animal models such as loss of function mutations in kit receptor [78] and 11beta-hydroxysteroid dehydrogenase 1 (11 β-HSD1) enzyme [79] or in some mouse strains such as C3H/HeJ [80].…”

Section: Does Clinical Evidence Support a Role For Adipocytes In Skelmentioning

confidence: 99%

Bone Marrow Adipose Tissue and Skeletal Health

Muruganandan

Govindarajan

Sinal

2018

Curr Osteoporos Rep

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Purpose of Review To summarize and discuss recent progress and novel signaling mechanisms relevant to bone marrow adipocyte formation and its physiological/pathophysiological implications for bone remodeling. Recent Findings Skeletal remodeling is a coordinated process entailing removal of old bone and formation of new bone. Several bone loss disorders such as osteoporosis are commonly associated with increased bone marrow adipose tissue. Experimental and clinical evidence supports that a reduction in osteoblastogenesis from mesenchymal stem cells at the expense of adipogenesis, as well as the deleterious effects of adipocyte-derived signaling, contributes to the etiology of osteoporosis as well as bone loss associated with aging, diabetes mellitus, post-menopause, and chronic drug therapy. However, this view is challenged by findings indicating that, in some contexts, bone marrow adipose tissue may have a beneficial impact on skeletal health. Summary Further research is needed to better define the role of marrow adipocytes in bone physiology/pathophysiology and to determine the therapeutic potential of manipulating mesenchymal stem cell differentiation.

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“…(62) In humans, some studies suggest that marrow adiposity occurs in response to TZDs, although in others this was not found. (63, 64)…”

Section: Overview and Fundamental Questionsmentioning

confidence: 99%

The bone–fat interface: basic and clinical implications of marrow adiposity

Devlin

Rosen

2015

The Lancet Diabetes & Endocrinology

213

159

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Obesity and osteoporosis are two of the most common chronic disorders of the 21st century. Both are accompanied by significant morbidity. The only place in the mammalian organism where bone and fat lie adjacent to each other is in the bone marrow. Marrow adipose tissue is a dynamic depot that likely exists as both constitutive and regulated compartments. Adipocytes secrete cytokines and adipokines that either stimulate or inhibit adjacent osteoblasts. The relationship of marrow adipose to other fat depots is complex and may play very distinct roles in modulating metabolic homeostasis, hematopoiesis and osteogenesis. Understanding the relationship between bone and fat cells that arise from the same progenitor within the ‘niche’ provides insight into the pathophysiology of age-related osteoporosis, diabetes mellitus and obesity.

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Pioglitazone increases bone marrow fat in type 2 diabetes: results from a randomized controlled trial

Cited by 47 publications

References 19 publications

Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice

Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice

Bone Marrow Adipose Tissue and Skeletal Health

The bone–fat interface: basic and clinical implications of marrow adiposity

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