Elsevier

Bone

Volume 91, October 2016, Pages 152-158
Bone

Full Length Article
Teriparatide in patients with osteoporosis and type 2 diabetes

https://doi.org/10.1016/j.bone.2016.06.017Get rights and content

Highlights

  • Few data are available regarding the effects of osteoporosis treatments on patients with diabetes at risk for fracture

  • DANCE was an uncontrolled observational study of patients treated with teriparatide as prescribed by their physician

  • This post hoc analysis of DANCE compared outcomes in patients with type 2 diabetes and without diabetes

  • During teriparatide treatment, changes in nonvertebral fracture incidence, BMD and back pain were similar between groups

Abstract

Despite evidence for higher fracture risk, clinical effects of osteoporosis treatments in type 2 diabetes (T2D) are largely unknown. Post hoc analyses of the DANCE observational study compared T2D patients and patients without diabetes to assess the effect of teriparatide, an osteoanabolic therapy on skeletal outcomes and safety. Patients included ambulatory men and women with osteoporosis receiving teriparatide 20 μg/day SQ up to 24 months followed by observation up to 24 months. Main outcome measures included nonvertebral fracture incidence comparing 0–6 months with 6 + months of teriparatide, change from baseline in BMD and back pain severity, and serious adverse events. Analyses included 4042 patients; 291 with T2D, 3751 without diabetes. Treatment exposure did not differ by group. For T2D patients, fracture incidence was 3.5 per 100 patient-years during 0–6 months treatment, and 1.6 during 6 months to treatment end (47% of baseline, 95% CI 12–187%); during similar periods, for patients without diabetes, fracture incidence was 3.2 and 1.8 (57% of baseline, 95% CI 39–83%). As determinants of fracture outcome during teriparatide treatment, diabetes was not a significant factor (P = 0.858), treatment duration was significant (P = 0.003), and the effect of duration was not significantly different between the groups (interaction P = 0.792). Increases in spine and total hip BMD did not differ between groups; increase in femoral neck BMD was greater in T2D patients than in patients without diabetes (+ 0.34 and + 0.004 g/cm2, respectively; P = 0.014). Back pain severity decreased in both groups. Teriparatide was well tolerated without new safety findings. In conclusion, during teriparatide treatment, reduction in nonvertebral fracture incidence, increase in BMD, and decrease in back pain were similar in T2D and non-diabetic patients.

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:

  • AV Schwartz has received a speaker's honorarium from Chugai Pharmaceutical Company and has served on an advisory board for Janssen Pharmaceuticals Inc.

  • I Pavo, J Alam, D Disch, D Schuster, and JH Krege are employees and shareholders of Eli Lilly and Company.

  • 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.

References (40)

  • E. de Waard et al.

    Increased fracture risk in patients with type 2 diabetes mellitus: an overview of the underlying mechanisms and the usefulness of imaging modalities and fracture risk assessment tools

    Maturitas

    (2014)
  • P. Gerdhem

    Osteoporosis and fragility fractures

    Best Pract. Res. Clin. Rheumatol.

    (2013)
  • P. Vestergaard

    Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes-a meta-analysis

    Osteoporos. Int.

    (2007)
  • M. Janghorbani et al.

    Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture

    Am. J. Epidemiol.

    (2007)
  • N. Napoli et al.

    Risk factors for subtrochanteric and diaphyseal fractures: The study of osteoporotic fractures

    J. Clin. Endocrinol. Metab.

    (2013)
  • L. Ma et al.

    Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies

    Eur. J. Epidemiol.

    (2012)
  • A.V. Schwartz et al.

    Study of Osteoporotic Fractures (SOF) Research Group; Osteoporotic Fractures in Men (MrOS) Research Group; Health, Aging, and Body Composition (Health ABC) Research Group; Health, Aging, and Body Composition (Health ABC) Research Group. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes

    JAMA

    (2011)
  • J.A. Kanis et al.

    Interpretation and use of FRAX in clinical practice

    Osteoporos. Int.

    (2011)
  • L.M. Giangregorio et al.

    FRAX underestimates fracture risk in patients with diabetes

    J. Bone Miner. Res.

    (2012)
  • W.D. Leslie et al.

    Does diabetes modify the effect of FRAX risk factors for predicting major osteoporotic and hip fracture?

    Osteoporos. Int.

    (2014)
  • V. Carnevale et al.

    Bone damage in type 2 diabetes mellitus

    Nutr. Metab. Cardiovasc. Dis.

    (2014)
  • P. Jackuliak et al.

    Osteoporosis, fractures, and diabetes

    Int. J. Endocrinol.

    (2014)
  • W. Yan et al.

    Impact of diabetes and its treatments on skeletal diseases

    Front. Med.

    (2013)
  • J.S. Manavalan et al.

    Circulating osteogenic precursor cells in type 2 diabetes mellitus

    J. Clin. Endocrinol. Metab.

    (2012)
  • J.M. Patsch et al.

    Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures

    J. Bone Miner. Res.

    (2013)
  • W.D. Leslie et al.

    TBS (trabecular bone score) and diabetes-related fracture risk

    J. Clin. Endocrinol. Metab.

    (2013)
  • R. Dhaliwal et al.

    Bone quality assessment in type 2 diabetes mellitus

    Osteoporos. Int.

    (2014)
  • J.N. Farr et al.

    In vivo assessment of bone quality in postmenopausal women with type 2 diabetes

    J. Bone Miner. Res.

    (2014)
  • M. Saito et al.

    Diabetes, collagen, and bone quality

    Curr. Osteoporos. Rep.

    (2014)
  • S. Ishii et al.

    Diabetes and femoral neck strength: findings from the hip strength across the menopausal transition study

    J. Clin. Endocrinol. Metab.

    (2012)
  • Cited by (70)

    • Contributors to impaired bone health in type 2 diabetes

      2023, Trends in Endocrinology and Metabolism
    • Assessment and treatment of osteoporosis and fractures in type 2 diabetes

      2022, Trends in Endocrinology and Metabolism
      Citation Excerpt :

      There are no subgroup analyses of subjects with T2D from the teriparatide RCT, which showed significant hip and spine BMD gains and vertebral and nonvertebral fracture reduction [91]. In a post hoc analysis of an observational study (DANCE), subjects with T2D had similar/greater improvements in BMD and similar reduction in nonvertebral fractures [92]. Bone anabolic effects may be particularly effective, given the low bone turnover state of T2D.

    • Osteoporosis and diabetes

      2021, Medecine des Maladies Metaboliques
    • Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel

      2021, Nutrition, Metabolism and Cardiovascular Diseases
      Citation Excerpt :

      These differences in nonvertebral fracture prevention between diabetic and non-diabetic women were mostly observed in the second year of treatment but did not continue over the long-term during the 7-years FREEDOM extension, nor were replicated in the crossover placebo to denosumab group. The skeletal effects of osteoanabolic therapy with teriparatide (a PTH 1–34 analog) in T2D patients were first evaluated by a post-hoc analysis of a single, non-randomized, observational study, the Direct Analysis of Nonvertebral Fractures in the Community Experience (DANCE) osteoporosis study [180]. Patients included ambulatory men and women with osteoporosis receiving teriparatide 20 μg/day up to 24 months followed by observation up to 24 months.

    • Postmenopausal osteoporosis coexisting with other metabolic diseases: Treatment considerations

      2021, Maturitas
      Citation 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].

    View all citing articles on Scopus
    View full text