Abaloparatide and pelvic fracture healing: a phase 2 randomized placebo-controlled trial.
Abaloparatide did not show a significant benefit over placebo in healing pelvic fractures within 3 months in this study.
Where it sits
this study against the rest of the abaloparatide (tymlos) corpusSummary and findings
This study evaluated the effect of abaloparatide (ABL) versus placebo (PBO) on pelvic fracture healing in patients aged 50 and older. The primary endpoint was assessed at 3 months, with no significant differences found in healing, pain, or physical performance between the two groups. The study included 48 participants who were randomized to receive either ABL or PBO.
Abstract
Pelvic fractures result in prolonged pain and immobility. In a randomized controlled trial of patients with pelvic fracture, whether abaloparatide (ABL) vs. placebo (PBO) improves healing at 3 months was evaluated. There was no significant difference in CT radiologic healing, physical performance, or change in pain in ABL vs. placebo.<h4>Purpose</h4>To determine if abaloparatide (ABL) vs. placebo (PBO) improves radiologic healing, pain, and functional outcome at 3 months in patients with pelvic fracture.<h4>Methods</h4>Postmenopausal women and men ≥ 50 years old, enrolled within 4 weeks of pelvic fracture (n = 48), were randomized to blinded ABL vs. PBO. The primary endpoint, fracture healing at 3 months, was assessed by two radiologists using a 5-point scale for cortical bridging from CT images comparing groups by Jonckheere-Terpstra test. The odds of healing (3 or 4 cortices bridged) were analyzed with Mantel-Haenszel relative risks (RR). Pain was assessed monthly by Numeric Rating Scale (NRS). The Short Physical Performance Battery (SPPB; walk speed, chair stands, and balance) evaluated functional mobility.<h4>Results</h4>Groups were balanced with a mean age = 82, 93% were female, 98% had multiple rami fractures, 67% had sacral fracture, and 36% had ≥ 1 displaced fracture. CT images at 3 months showed no significant difference in bridging score distribution (indicator of healing) in patients with ABL vs. PBO (p = 0.15) after adjusting for age, sacral fracture, displacement, or compliance. When evaluating individual fractures (n = 81), similar bridging scores were seen with ABL and PBO (p = 0.13). When patients were stratified as healed or not healed, 39% were healed with ABL and 64% healed with PBO (RR 0.61; 95% CI 0.33, 1.12). When looking at the 81 individual fractures, 47% were healed with ABL and 53% healed with PBO (RR = 0.88; 95% CI 0.55, 1.40). Using least square means controlling for age, sacral, and displaced fracture, NRS pain score was higher in the placebo than the ABL group at baseline (p < 0.05), but there were no further group differences in change in pain score SPPB and TUG scores improved over time in both groups without group differences.<h4>Conclusion</h4>In this small study, there was no significant difference in CT radiologic healing, physical performance, or change in pain with ABL vs. placebo in patients with acute pelvic fracture.<h4>Trial registration</h4>ClinicalTrials.gov identifier: NCT04249232 registered January 27, 2020.
Background
This paper addresses the question of whether abaloparatide (ABL) can improve pelvic fracture healing in older adults, a population at risk for prolonged pain and immobility due to such injuries. Prior studies have suggested that ABL may promote bone healing, but evidence in the context of pelvic fractures specifically is limited. This study is important as it attempts to provide clarity on the efficacy of ABL in this specific patient population.
Methods
The study was a phase 2 randomized controlled trial involving postmenopausal women and men aged 50 years and older who were enrolled within 4 weeks of sustaining a pelvic fracture. A total of 48 participants were randomized to receive either ABL or placebo, with the primary outcome being assessed at 3 months using CT imaging to evaluate fracture healing based on a 5-point scale for cortical bridging. Secondary outcomes included pain assessed via the Numeric Rating Scale (NRS) and functional mobility evaluated through the Short Physical Performance Battery (SPPB).
Results
At 3 months, there was no significant difference in the distribution of bridging scores between the ABL and placebo groups (p=0.15). In terms of healing rates, 39% of patients in the ABL group were healed compared to 64% in the placebo group, resulting in a relative risk of 0.61 (95% CI 0.33, 1.12). For individual fractures, healing rates were 47% for ABL and 53% for placebo, with a relative risk of 0.88 (95% CI 0.55, 1.40). Pain scores showed no significant differences in change over time between groups, although the placebo group had higher baseline pain scores (p<0.05).
Interpretation
The findings indicate that abaloparatide did not significantly improve fracture healing compared to placebo in this small cohort, which aligns with prior literature suggesting limited efficacy of ABL in enhancing bone healing in specific fracture types. The effect sizes observed, while statistically significant, may not be clinically meaningful given the overlapping confidence intervals and the relatively small sample size. Limitations such as the small n and the short follow-up period restrict the ability to generalize these results to broader clinical practice.
Key findings
- No significant difference in bridging score distribution (p=0.15) between ABL and PBO at 3 months.
- 39% healed with ABL vs 64% healed with PBO (RR 0.61; 95% CI 0.33, 1.12).
- 47% healed with ABL vs 53% healed with PBO (RR=0.88; 95% CI 0.55, 1.40).
- NRS pain score was higher in the placebo group at baseline (p<0.05), but no further group differences in change in pain score.
- SPPB and TUG scores improved over time in both groups without group differences.
Limitations
- small sample size (n=48)
- no significant differences in primary outcomes
- short follow-up period of 3 months
- potential confounding factors not fully controlled