Interim Effects of Zoledronate, Denosumab, or Teriparatide on Bone Microarchitecture in Type 2 Diabetes: A Pilot
Trupti N Prasad1, Rimesh Pal1, Sanjay K Bhadada1
1Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
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.
Insights
Teriparatide improved bone microarchitecture in postmenopausal women with type 2 diabetes (T2D). Denosumab showed modest bone stiffness improvements, highlighting the need for larger studies on T2D pharmacologic management.
Area of Science:
- Endocrinology
- Bone Biology
- Pharmacology
Background:
- Type 2 diabetes (T2D) elevates fracture risk due to compromised bone microarchitecture, even with normal bone density.
- Limited evidence exists for effective pharmacologic treatments targeting diabetic bone disease.
Purpose of the Study:
- To assess the interim effects of zoledronate, denosumab, and teriparatide on bone microarchitecture in postmenopausal women with T2D.
- To compare these effects against standard care in a high-fracture-risk population.
Main Methods:
- A 72-week, randomized, open-label pilot trial involving 129 postmenopausal women with T2D.
- Interventions included zoledronate, denosumab, teriparatide, or standard care (calcium/cholecalciferol).
- Bone microarchitecture was evaluated using HR-pQCT, with bone turnover markers assessed at 24 weeks.
Main Results:
- Teriparatide significantly enhanced bone microarchitecture, including total and trabecular volumetric bone mineral density (vBMD) and trabecular number.
- Denosumab improved tibial trabecular vBMD and number, with a modest increase in tibial stiffness.
- Zoledronate showed a minor improvement in tibial total vBMD; bone turnover markers indicated an anabolic window with teriparatide.
Conclusions:
- Teriparatide demonstrated early benefits for bone microarchitecture in postmenopausal women with T2D.
- Denosumab provided a modest increase in bone stiffness.
- Further large-scale studies are required to determine optimal therapeutic strategies for diabetic bone disease.
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