Effect of a Multifactorial Intervention on Fracture in Patients With Type 2 Diabetes: Subanalysis of the J-DOIT3 Study

Takayoshi Sasako, Kohjiro Ueki, Kana Miyake, Yukiko Okazaki, Yasuhiro Takeuchi, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki, Takayoshi Sasako, Kohjiro Ueki, Kana Miyake, Yukiko Okazaki, Yasuhiro Takeuchi, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki

Abstract

Aims: To evaluate the effects of an intensified multifactorial intervention and patient characteristics on the incidence of fractures comorbid with type 2 diabetes.

Methods: Fracture events were identified and analyzed among adverse events reported in the J-DOIT3 study, a multicenter, open-label, randomized, parallel-group trial that was conducted in Japan, in which patients with type 2 diabetes were randomly assigned to receive conventional therapy for glucose, blood pressure, and lipids (targets: HbA1c < 6.9%, blood pressure <130/80 mm Hg, LDL-cholesterol <120mg/dL) or intensive therapy (HbA1c < 6.2%, blood pressure <120/75 mm Hg, LDL-cholesterol <80mg/dL) (ClinicalTrials.gov registration no. NCT00300976).

Results: The cumulative incidence of fractures did not differ between those receiving conventional therapy and those receiving intensive therapy (hazard ratio (HR) 1.15; 95% CI, 0.91-1.47; P = 0.241). Among the potential risk factors, only history of smoking at baseline was significantly associated with the incidence of fractures in men (HR 1.96; 95% CI, 1.04-3.07; P = 0.038). In contrast, the incidence of fractures in women was associated with the FRAX score [%/10 years] at baseline (HR 1.04; 95% CI, 1.02-1.07; P < 0.001) and administration of pioglitazone at 1 year after randomization (HR 1.59; 95% CI, 1.06-2.38; P = 0.025).

Conclusions: Intensified multifactorial intervention may be implemented without increasing the fracture risk in patients with type 2 diabetes. The fracture risk is elevated in those with a history of smoking in men, whereas it is predicted by the FRAX score and is independently elevated with administration of pioglitazone in women.

Keywords: clinical trial; epidemiology; fracture risk assessment; osteoporosis; therapeutics; type 2 diabetes.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Cumulative incidence of fractures. Cumulative incidence of fractures in (A) both therapy groups, (B) both therapy groups stratified by sex, and (C) both sexes stratified by the FRAX score at baseline.
Figure 2.
Figure 2.
Histograms for the FRAX score at baseline in both therapy groups stratified by sex.

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Source: PubMed

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