Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial

Abstract

Pelvic fracture patients were randomized to blinded daily subcutaneous teriparatide (TPTD) or placebo to assess healing and functional outcomes over 3 months. With TPTD, there was no evidence of improved healing by CT or pain reduction; however, physical performance improved with TPTD but not placebo (group difference p < 0.03).

Introduction: To determine if teriparatide (20 μg/day; TPTD) results in improved radiologic healing, reduced pain, and improved functional outcome vs placebo over 3 months in pelvic fracture patients.

Methods: This randomized, placebo-controlled study enrolled 35 patients (women and men >50 years old) within 4 weeks of pelvic fracture and evaluated the effect of blinded TPTD vs placebo over 3 months on fracture healing. Fracture healing from CT images at 0 and 3 months was assessed as cortical bridging using a 5-point scale. The numeric rating scale (NRS) for pain was administered monthly. Physical performance was assessed monthly by Continuous Summary Physical Performance Score (based on 4 m walk speed, timed repeated chair stands, and balance) and the Timed Up and Go (TUG) test.

Results: The mean age was 82, and >80% were female. The intention to treat analysis showed no group difference in cortical bridging score, and 50% of fractures in TPTD-treated and 53% of fractures in placebo-treated patients were healed at 3 months, unchanged after adjustment for age, sacral fracture, and fracture displacement. Median pain score dropped significantly in both groups with no group differences. Both CSPPS and TUG improved in the teriparatide group, whereas there was no improvement in the placebo group (group difference p < 0.03 for CSPPS at 2 and 3 months).

Conclusion: In this small randomized, blinded study, there was no improvement in radiographic healing (CT at 3 months) or pain with TPTD vs placebo; however, there was improved physical performance in TPTD-treated subjects that was not evident in the placebo group.

Keywords: Fracture healing; Pain; Pelvic fracture; Physical performance; Placebo; Teriparatide.

Figure 1:

Consort diagram for the study

Figure 2:

Pain Scores – Average over last week using Least Square means at baseline 4, 8 and 12 weeks. p<0.05 versus baseline within each group; no group differences

Figure 3:

Physical Function Scores (CSPPS and TUG) in Placebo vs. Teriparatide at 4, 8 and 12 months after correcting for age, baseline SF-36 score and pain. For the CSPPS measure (a) there was a significant improvement within the TPTD group, but not in the placebo group. * p<0.01 TPTD 4-week vs 8 or 12 weeks; # p<0.03 between groups. The time in seconds to complete the Timed Up and Go (b) was improved within the TPTD group and not the placebo group. * p<0.005 TPTD 4-week vs 8 or 12 weeks (no group differences).