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Interim Effects of Zoledronate, Denosumab, or Teriparatide on Bone Microarchitecture in Type 2 Diabetes: A Pilot Trial.

  • 2025-11-03
  • The Journal of clinical endocrinology and metabolism 111(5)
    • Trupti N Prasad
    • Rimesh Pal
    • Sanjay K Bhadada
    • Sant Ram
    • Veenu Singla
    • Seema Pulami

Study Design

Type
Randomized Controlled Trial (RCT)
Population
129 postmenopausal women with T2D for more than 5 years and high fracture risk
Methods
72-week, randomized, open-label, blinded-end point (PROBE) pilot clinical trial; 1:1:1:1 ratio to receive zoledronate 5 mg annually, denosumab 60 mg every 6 months, teriparatide 20 µg daily, or only standard of care (calcium/cholecalciferol)
Blinding
Open-label
Duration
72 weeks
Funding
Unclear

Context

Type 2 diabetes (T2D) increases fragility fracture risk despite normal/elevated areal bone mineral density (aBMD), attributed to compromised bone microarchitecture. However, evidence guiding pharmacologic management of diabetic bone disease remains limited.

Objective

We aimed to evaluate interim effects of zoledronate, denosumab, or teriparatide on bone microarchitecture in postmenopausal women with T2D at high fracture risk.

Methods

A 72-week, randomized, open-label, blinded-end point (PROBE) pilot clinical trial (CTRI/2022/02/039978) was conducted at a single tertiary care center in India. Participants included 129 postmenopausal women with T2D for more than 5 years and high fracture risk (prior fragility fracture and/or T-score < -2.5 [corrected for T2D] with elevated FRAX®). Participants were randomly assigned in a 1:1:1:1 ratio to receive zoledronate 5 mg annually, denosumab 60 mg every 6 months, teriparatide 20 µg daily, or only standard of care (calcium/cholecalciferol) for 72 weeks. The outcome measure included a prespecified 24-week interim exploratory analysis focusing on changes in bone microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal tibia and radius. Bone turnover markers (BTMs) were also evaluated.

Results

Baseline demographic, biochemical, aBMD, and HR-pQCT parameters were comparable across groups. Teriparatide significantly improved total and trabecular volumetric BMD (vBMD) (at tibia and radius), trabecular number (Tb.N), trabecular bone volume fraction (BV/TV) (at tibia), and trabecular thickness (Tb.Th) (at radius). Denosumab improved tibial trabecular vBMD and Tb.N. Zoledronate improved only tibial total vBMD. Microfinite element analysis-derived strength parameters were unchanged, except for a modest increase in tibial stiffness with denosumab. BTMs decreased with antiresorptives, increased with teriparatide, and showed an anabolic window by 6 weeks.

Conclusion

Teriparatide demonstrated early improvements in bone microarchitecture in postmenopausal women with T2D while denosumab showed a modest increase in bone stiffness at the distal tibia. Larger, adequately powered studies are needed to clarify the relative effects of anabolic and antiresorptive therapies in this population.

Research Insights

  • Calcium→Improved Bone Mineral Density

    Zoledronate improved only tibial total vBMD.

    Effect
    Neutral
    Effect size
    Small
    Dose
    standard of care (calcium/cholecalciferol) – specific dose not stated
  • Calcium→Improved Total Volumetric Bone Mineral Density

    Zoledronate improved only tibial total vBMD. Teriparatide significantly improved total and trabecular volumetric BMD...

    Effect
    Neutral
    Effect size
    Small
    Dose
    standard of care (calcium/cholecalciferol) – specific dose not stated
  • Calcium→Improved Trabecular Number

    Teriparatide significantly improved... trabecular number (Tb.N)... Denosumab improved tibial... Tb.N.

    Effect
    Neutral
    Effect size
    Small
    Dose
    standard of care (calcium/cholecalciferol) – specific dose not stated
  • Vitamin D→Improved Bone Mineral Density

    Zoledronate improved only tibial total vBMD.

    Effect
    Neutral
    Effect size
    Small
    Dose
    standard of care (calcium/cholecalciferol) – specific dose not stated
  • Vitamin D→Improved Total Volumetric Bone Mineral Density

    Zoledronate improved only tibial total vBMD. Teriparatide significantly improved total and trabecular volumetric BMD...

    Effect
    Neutral
    Effect size
    Small
    Dose
    standard of care (calcium/cholecalciferol) – specific dose not stated
  • Vitamin D→Improved Trabecular Number

    Teriparatide significantly improved... trabecular number (Tb.N)... Denosumab improved tibial... Tb.N.

    Effect
    Neutral
    Effect size
    Small
    Dose
    standard of care (calcium/cholecalciferol) – specific dose not stated
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