Full Length ArticleTeriparatide in patients with osteoporosis and type 2 diabetes
Introduction
Type 2 diabetes is associated with greater fracture risk [1], [2], [3] but paradoxically with average or higher bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) [1], [4]. As a result, although BMD is a strong predictor of fracture in those with diabetes, BMD T-score tends to underestimate risk compared with patients without diabetes [5]. FRAX®, a tool to estimate 10-year fracture probability from clinical risk factors, including BMD [6], also underestimates fracture risk in patients with type 2 diabetes [5], [7], [8]. Hence, for the patient with type 2 diabetes, it has recently been suggested that bone health assessment and fracture risk prediction should address bone quality as well as bone density [9], [10], [11], [12]. The underlying reasons for increased bone fragility with diabetes are a topic of intense investigation [13], [14], [15], [16], [17], [18], [19], [20]. Despite evidence for increased bone fragility in type 2 diabetes, little is known about the skeletal effects of osteoporosis treatments in patients with type 2 diabetes. Clinical studies of the effects of teriparatide in particular are not available. Limited evidence from rodent models of type 2 diabetes suggests that PTH improves bone mass and strength in the setting of diabetes [21], [22], but that efficacy may be lower compared with controls [22].
The Direct Analysis of Nonvertebral Fractures in the Community Experience (DANCE) osteoporosis study affords an opportunity to address this question by exploring skeletal outcomes in patients with osteoporosis and type 2 diabetes treated with teriparatide, an osteoanabolic therapy. Teriparatide is indicated for 1) treatment of postmenopausal women with osteoporosis at high risk for fracture, 2) increase of bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture, and 3) treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture [23].
The DANCE study (NCT01078805), an open-label, prospective, multicenter observational study, enrolled ambulatory women and men with osteoporosis at high risk for fracture who were prescribed teriparatide by their physician [24], [25], [26]. The primary objective was to evaluate the occurrence of nonvertebral fractures in patients treated with teriparatide for up to 24 months in a community-based setting. Secondary objectives included assessments of BMD, back pain, and serious adverse events. Here we report the outcomes for the subset of patients with type 2 diabetes.
Section snippets
Materials and methods
The purpose of this analysis was to assess the incidence of new nonvertebral fragility fracture, changes in BMD, severity of back pain, and safety in patients with type 2 diabetes receiving treatment with teriparatide in the DANCE study.
Baseline patient characteristics
Fig. 1 provides the disposition of study patients. From the overall DANCE study enrollment (N = 4167) [24], 4085 received ≥ 1 dose of teriparatide, including 291 patients with type 2 diabetes and 3751 patients without diabetes; 43 patients with type 1 diabetes were excluded. After one year, 2546 patients remained on teriparatide treatment, including 171 with type 2 diabetes and 2375 without diabetes (Fig. 2). Investigators recorded 2099 patients completed the study: 133 with type 2 diabetes and
Discussion
This is the first report of teriparatide treatment in patients with type 2 diabetes and osteoporosis, a population at increased risk for fracture. During teriparatide, lower incidence of nonvertebral fractures over time, increase in BMD, and reduced back pain were similar in patients with type 2 diabetes and in patients without diabetes.
The justification for comparing the incidence of nonvertebral fractures during the first 6 months of teriparatide treatment with the fracture incidence occurring
Conflict of interest
The authors have the following disclosures:
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AV Schwartz has received a speaker's honorarium from Chugai Pharmaceutical Company and has served on an advisory board for Janssen Pharmaceuticals Inc.
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I Pavo, J Alam, D Disch, D Schuster, and JH Krege are employees and shareholders of Eli Lilly and Company.
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JM Harris is an employee of Eli Lilly and Company.
The study was funded by Eli Lilly and Company.
Acknowledgments
The clinical study described herein was funded by Eli Lilly and Company. The authors acknowledge Ke Wu, an employee of Eli Lilly and Company, for assistance with statistical analysis, and Thomas Melby, an employee of inVentiv Health Clinical, for editorial assistance.
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2021, MaturitasCitation Excerpt :Since T2DM is characterized by low bone turnover [45], anabolic medications, which stimulate bone formation, may have an advantage over antiresorptives, at least from a pathophysiological point of view. In patients with T2DM, teriparatide treatment achieved similar increases in lumbar spine (LS) and total hip (TH) BMD, but higher increases in femoral neck (FN) BMD, along with comparable non-vertebral fracture incidence compared to patients without T2DM [46]. In women with T2DM, abaloparatide, a parathyroid hormone related peptide analog available in the US but not in EU, significantly increased BMD at LS, FN and TH, and trabecular bone score (TBS) and reduced fracture incidence as compared with placebo [47].