DPP-4 inhibitor therapy and bone fractures in people with Type 2 diabetes – A systematic review and meta-analysis

Mamza, Jil; Marlin, Carol; Cai, Wei; Chokkalingam, Kamal; Idris, Iskandar

doi:10.1016/j.diabres.2016.04.029

Cited by 53 publications

(42 citation statements)

References 59 publications

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“…This finding was also proved by another meta-analysis reported by Mamza et al (2016) and a retrospective population-based cohort study (Driessen et al, 2017). …”

Section: Effect Of Dpp-4is On Fracture Risksupporting

confidence: 66%

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Metabolism and the Possible Underlying Mechanisms

et al. 2017

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Diabetes mellitus has been demonstrated to be closely associated with osteoporosis. Accordingly, hypoglycemic therapy is considered effective in treating metabolic bone disease. Recently, the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, a new type of antidiabetic drug, on bone metabolism have been widely studied. This review mainly describes the effects of DPP-4 inhibitors on bone metabolism, including their effects on bone mineral density, bone quality, and fracture risk. In addition, the potential underlying mechanisms are discussed. Based on the current progress in this research field, DPP-4 inhibitors have been proved to reduce fracture risk. In addition, sitagliptin, a strong and highly selective DPP-4 inhibitor, showed its beneficial effects on bone metabolism by improving bone mineral density, bone quality, and bone markers. With regard to the potential underlying mechanisms, DPP-4 inhibitors may promote bone formation and reduce bone resorption through DPP-4 substrates and DPP-4-related energy metabolism. Vitamin D and other related signaling pathways also play a role in affecting bone metabolism. Although these assumptions are controversial, they provide a translational pharmacology approach for the clinical use of DPP-4 inhibitors in the treatment of metabolic diseases. Prior to the use of these drugs in clinic, further studies should be conducted to determine the appropriate type of DPP-4 inhibitor, the people who would benefit the most from this therapy, appropriate dose and duration, and the effects of the treatment.

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“…This finding was also proved by another meta-analysis reported by Mamza et al (2016) and a retrospective population-based cohort study (Driessen et al, 2017). …”

Section: Effect Of Dpp-4is On Fracture Risksupporting

confidence: 66%

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Metabolism and the Possible Underlying Mechanisms

et al. 2017

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“…An initial meta-analysis that included 28 randomised clinical trials of DPP-4 inhibitor therapies reported a protective effect on fractures, identified through serious adverse event reports [58]. However, this appears to have been a chance finding as subsequent meta-analyses, incorporating additional RCTs, found no evidence of an effect of DPP-4 inhibitor therapy on fractures [59,60]. For example, the largest published meta-analysis included 62 RCTs of DPP-4 inhibitor therapies with 722 fractures and reported a relative risk of 0.95 (95% CI [62,63].…”

Section: Effects Of Glucose-lowering Medications On Bmd and Fracture mentioning

confidence: 99%

Diabetes, bone and glucose-lowering agents: clinical outcomes

Schwartz

2017

Diabetologia

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Older adults with diabetes are at higher risk of fracture and of complications resulting from a fracture. Hence, fracture risk reduction is an important goal in diabetes management. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Beata Lecka-Czernik (DOI 10.1007/s00125-017-4269-4). Specifically, this review discusses the challenges of accurate fracture risk assessment in diabetes. Standard tools for risk assessment can be used to predict fracture but clinicians need to be aware of the tendency for the bone mineral density Tscore and the fracture risk assessment tool (FRAX) to underestimate risk in those with diabetes. Diabetes duration, complications and poor glycaemic control are useful clinical markers of increased fracture risk. Glucose-lowering agents may also affect fracture risk, independent of their effects on glycaemic control, as seen with the negative skeletal effects of the thiazolidinediones; in this review, the potential effects of glucose-lowering medications on fracture risk are discussed. Finally, the current understanding of effective fracture prevention in older adults with diabetes is reviewed.

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“…In contrast, two recent meta-analyses assessing DPP-4 inhibitor use and fracture risk failed to find an association. Fu et al compared 62 eligible RCTs with 62,206 participants, including 33,452 patients treated with DPP-4 inhibitors; they found that DPP-4 inhibitor use does not modify the risk of bone fracture compared with placebo or other anti-diabetic medications in patients with type 2 diabetes [43, 44]. Similarly, Mamza et al, identified 51 eligible RCTs for meta-analysis ( N = 36,402) for comparison [44].…”

Section: Discussionmentioning

confidence: 99%

“…Fu et al compared 62 eligible RCTs with 62,206 participants, including 33,452 patients treated with DPP-4 inhibitors; they found that DPP-4 inhibitor use does not modify the risk of bone fracture compared with placebo or other anti-diabetic medications in patients with type 2 diabetes [43, 44]. Similarly, Mamza et al, identified 51 eligible RCTs for meta-analysis ( N = 36,402) for comparison [44]. Thirty-seven of these studies compared DPP-4 inhibitor with placebo ( n = 23,974), while 14 studies ( n = 12,428) compared DPP-4 inhibitor with an active comparator: there was no significant association between DPP-4 inhibitor use and the incidence of fractures [44].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Mamza et al, identified 51 eligible RCTs for meta-analysis ( N = 36,402) for comparison [44]. Thirty-seven of these studies compared DPP-4 inhibitor with placebo ( n = 23,974), while 14 studies ( n = 12,428) compared DPP-4 inhibitor with an active comparator: there was no significant association between DPP-4 inhibitor use and the incidence of fractures [44]. In a population-based cohort study from the UK Clinical Practice Research Datalink (CPRD) including over 200,000 patients with diabetes, DPP-4 inhibitors were not associated with fracture risk [23].…”

Section: Discussionmentioning

confidence: 99%

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Association of DPP-4 activity with BMD, body composition, and incident hip fracture: the Cardiovascular Health Study

et al. 2017

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Summary There was no association of plasma DPP-4 activity levels with bone mineral density (BMD), body composition, or incident hip fractures in a cohort of elderly community-dwelling adults. Introduction Dipeptidyl peptidase IV (DPP-4) inactivates several key hormones including those that stimulate postprandial insulin secretion, and DPP-4 inhibitors (gliptins) are approved to treat diabetes. While DPP-4 is known to modulate osteogenesis, the relationship between DPP-4 activity and skeletal health is uncertain. The purpose of the present study was to examine possible associations between DPP-4 activity in elderly subjects enrolled in the Cardiovascular Health Study (CHS) and BMD, body composition measurements, and incident hip fractures. Methods All 1536 male and female CHS participants who had evaluable DXA scans and plasma for DPP-4 activity were included in the analyses. The association between (1) BMD of the total hip, femoral neck, lumbar spine, and total body; (2) body composition measurements (% lean, % fat, and total body mass); and (3) incident hip fractures and plasma levels of DPP-4 activity were determined. Results Mean plasma levels of DPP-4 activity were significantly higher in blacks (227 ± 78) compared with whites (216 ± 89) (p = 0.04). However, there was no significant association of DPP-4 activity with age or gender (p ≥ 0.14 for both). In multivariable adjusted models, there was no association of plasma DPP-4 activity with BMD overall (p ≥ 0.55 for all) or in gender stratified analyses (p ≥ 0.23). There was also no association of DPP-4 levels and incident hip fractures overall (p ≥ 0.24) or in gender stratified analyses (p ≥ 0.39). Conclusion Plasma DPP-4 activity, within the endogenous physiological range, was significantly associated with race, but not with BMD, body composition, or incident hip fractures in elderly community-dwelling subjects.

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DPP-4 inhibitor therapy and bone fractures in people with Type 2 diabetes – A systematic review and meta-analysis

Cited by 53 publications

References 59 publications

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Metabolism and the Possible Underlying Mechanisms

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Metabolism and the Possible Underlying Mechanisms

Diabetes, bone and glucose-lowering agents: clinical outcomes

Association of DPP-4 activity with BMD, body composition, and incident hip fracture: the Cardiovascular Health Study

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