THU426 Randomized Controlled Trial Comparing The Efficacy Of Teriparatide, Zoledronate And Denosumab In Postmenopausal Women With Type 2 Diabetes Mellitus At High Risk Of Fragility Fractures: 6-month Interim Analysis Of HR-pQCT Parameters
Authors: Pal Rimesh , Prasad Trupti Nagendra , Bhadada Sanjay Kumar , Singla Veenu , Ram Sant , Aggarwal Neelam , Kumar Ashok 
Published: October 2023

Disclosure: R. Pal: None. T.N. Prasad: None. S.K. Bhadada: None. V. Singla: None. S. Ram: None. N. Aggarwal: None. A. Kumar: None.

People with type 2 diabetes (T2D) are at high-risk of fragility fractures, however, there are no randomised controlled trials (RCTs) evaluating the efficacy/safety of anti-osteoporosis drugs as a primary endpoint in T2D (1). To address this lacuna, we conducted a pilot prospective, open-labeled, blinded-end point (PROBE) RCT (CTRI/2022/02/039978) wherein consecutive postmenopausal female (≥ 50 years) with T2D (duration ≥ 5 years) were screened. Subjects with HbA1c 7-10%, eGFR &gt; 45 ml/min/1.73 m2 and prior history of vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or at high-risk of fragility fractures [defined as areal bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ≤ -2.5 and high FRAX score] and without any secondary cause of osteoporosis were randomised in staggered fashion in a 1:1:1:1 ratio to receive either daily teriparatide, yearly zoledronate, biannually denosumab (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary end points were change in areal BMD and frequency of incident fractures at 18 months. The secondary end point was change in HR-pQCT parameters measured at distal radius and distal tibia (XtremeCT II, SCANCO Medical AG, Switzerland) at 6 and 18 months.Out of 412 participants who were screened, 104 subjects were randomized to any of the 4 arms. Out of these 104 subjects, 53 have completed 6 months of follow-up (teriparatide n=14, zoledronate n=14, denosumab n=15, control n=10). There were no statistically significant differences in age, HbA1c, eGFR, calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone, procollagen type I N-propeptide (PINP), C-terminal telopeptide (CTX), areal BMD, trabecular bone score (TBS), FRAX score or HR-pQCT parameters between the 4 groups at randomisation. At 6 months, there was no significant difference in HbA1c between the 4 groups; PINP and CTX rise was significantly higher in teriparatide arm compared to zoledronate, denosumab or control arms. With regard to HR-pQCT, there were no statistically significant differences in total [total volumetric BMD (vBMD), bone volume fraction], cortical (vBMD, thickness, porosity, pore diameter), or trabecular (vBMD, thickness, number, separation) bone properties at the distal radius and distal tibia between the 4 arms at 6 months of follow-up. To conclude, zoledronate, denosumab or teriparatide were unable to induce any significant microarchitectural changes than standard of care in postmenopausal women with T2D at high-risk of fragility fractures following 6 months of treatment. Longer duration of treatment and follow-up of the cohort is required to arrive at robust conclusions.

Reference: (1) Pal et al., Bone fragility in type 2 diabetes mellitus: a lot left to explore. Nat Rev Endocrinol. 2022;18:651-651

Presentation: Thursday, June 15, 2023