Thiazolidinediones and Fractures in Men and Women

Dormuth, Colin R.; Carney, Greg; Carleton, Bruce; Bassett, Ken; Wright, James M

doi:10.1001/archinternmed.2009.214

Cited by 126 publications

(89 citation statements)

References 31 publications

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“…Our data indeed show that in contrast to MET, serum sclerostin levels increased in patients treated with PIO and that this was associated with a significant increase in serum CTX levels, despite adequate glycemic control. Over the past decade, evidence has been accumulating on the detrimental effect of TZDs on the skeleton, decreasing bone mass and increasing fracture risk in both men (33,34,35) and women with diabetes mellitus (4,33,35,36,37,38,39). This deleterious effect of TZDs on the skeleton is generally attributed to the activation of PPARg in the bone marrow by these agents, leading to preferential stimulation of adipogenesis at the cost of osteoblastogenesis (5).…”

Section: Discussionmentioning

confidence: 99%

Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus

Lierop

Hamdy

Meer

et al. 2012

European Journal of Endocrinology

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Objective: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the expression of sclerostin, a negative regulator of bone formation, in vitro. Abnormal sclerostin production may, therefore, be involved in the pathogenesis of increased bone fragility in patients with T2DM treated with TZDs. Methods: We measured serum sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in 71 men with T2DM treated with either pioglitazone (PIO) (30 mg once daily) or metformin (MET) (1000 mg twice daily). Baseline values of sclerostin and P1NP were compared with those of 30 healthy male controls. Results: Compared with healthy controls, patients with T2DM had significantly higher serum sclerostin levels (59.9 vs 45.2 pg/ml, P!0.001) but similar serum P1NP levels (33.6 vs 36.0 ng/ml, PZ0.39). After 24 weeks of treatment, serum sclerostin levels increased by 11% in PIO-treated patients and decreased by 1.8% in MET-treated patients (PZ0.018). Changes in serum sclerostin were significantly correlated with changes in serum CTX in all patients (rZ0.36, PZ0.002) and in PIO-treated patients (rZ0.39, PZ0.020), but not in MET-treated patients (rZ0.17, PZ0.31). Conclusions: Men with T2DM have higher serum sclerostin levels than healthy controls, and these levels further increase after treatment with PIO, which is also associated with increased serum CTX. These findings suggest that increased sclerostin production may be involved in the pathogenesis of increased skeletal fragility in patients with T2DM in general and may specifically contribute to the detrimental effect of TZDs on bone.

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Section: Discussionmentioning

confidence: 99%

Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus

Lierop

Hamdy

Meer

et al. 2012

European Journal of Endocrinology

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“…More recently, Habib et al [70] showed an increased risk in women >65 years, but not in men and Dormuth et al [71], showed a higher risk with pioglitazone, affecting men and women.…”

Section: Bone Fracturesmentioning

confidence: 98%

Diabetes-Old Therapies Revisited

Guimarães¹

2016

EMIJ

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Today, there are many therapeutic options for the treatment of type 2 Diabetes, which means that therapeutic decision making has become increasingly challenging and complex. With the recent introduction in clinical practice of new classes, with different mechanisms of action, what is the role of the older drugs? This article reviews these drugs, with recently published data update. Today, recommendations are not based on a simple algoritm, but in a patient centered approach. Besides the phenotypic heterogeneity of patients with type 2 diabetes, there is also a great diversity in response to treatment. This concept of personalized medicine has changed in recent years. The new era of personalized medicine evolves in order to identify molecular and clinical signs that can predict therapeutic response, reducing uncertainty in decision making. The "old" drugs may resurface, with more precise indications, in selected groups of patients.

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“…The pleiotropic effects of TZDs include decreasing insulin resistance, hyperplasia of pancreatic beta cells (potential to improve beta cell function), improve the lipid parameters, alteration in adipokines (increase the adiponectin, decrease resistin), decreasing C-reactive protein levels, improving endothelial function, reducing restenosis rates in subjects with coronary artery disease, mild improvement in blood pressure and decreasing urinary albumin excretion. However, epidemiological and observational studies indicate that TZD therapy with rosiglitazone and Pioglitazone is also associated with an increased risk of fractures [10][11][12][13][14][15]. TZDs improve glycemic control through activation of the peroxisome proliferator-activated receptor (PPAR)-γ. TZDs inhibit osteoblastogenesis [16][17][18] and suppress markers of osteoblast activity [16], and cause increased osteoclastogenesis [19], which results in decreased bone mass.…”

Section: Introductionmentioning

confidence: 99%