Neoadjuvant teriparatide therapy targeting the osteoporotic spine: influence of administration period from the perspective of bone histomorphometry

Abstract

OBJECTIVE Teriparatide (TPTD) is a potent promoter of early-stage osteogenesis and may be a useful adjuvant therapy to reduce complications related to bone fragility in spinal surgery patients with osteoporosis. However, effective neoadjuvant TPTD therapy regimens remain poorly understood. This study aimed to examine the effect of preoperative TPTD administration on cancellous bone with bone histomorphometry and to clarify the timing of preoperative TPTD administration for patients with spinal fusion and osteoporosis. METHODS In this longitudinal multicenter study, 57 patients with spinal fusion and osteoporosis, who consented to undergo iliac biopsy, were allocated to the following treatment groups: neoadjuvant TPTD therapy group (n = 42) and no neoadjuvant therapy (NTC) group (n = 15). Patients in the TPTD group were categorized into subgroups on the basis of duration of preoperative TPTD administration, as follows: 1 month (n = 9), 2 months (n = 8), 3 months (n = 9), 4 months (n = 7), and 6 months (n = 9). All patient samples were preoperatively double labeled with tetracycline, and iliac biopsies were performed during spinal fusion surgery. Histomorphometric analyses were performed on nondecalcified, thin-sliced specimens. Specimens were classified on the basis of TPTD administration duration and subsequently compared with those of the NTC group. Postoperative complications and Oswestry Disability Index scores were evaluated at 1 and 2 years after surgery. RESULTS There were no demographic differences between groups. Mineralizing surface/bone surface, a key parameter of dynamic bone formation, started to increase after 1 month of TPTD administration; this increase became significant after 3 months of administration and peaked at 4 months, with a 6-fold increase relative to that of the NTC group. The patients who received preoperative TPTD for 3 months or more had superior clinical results in terms of the osteoporotic complication rate and Oswestry Disability Index scores, except for bisphosphonate-pretreated patients. CONCLUSIONS When considering neoadjuvant TPTD therapy, the authors recommend at least 3 months of preoperative administration to provide a more substantial anabolic effect from the early postoperative stage.

Comparison of osteoanabolic agents (teriparatide and romosozumab) with bisphosphonates in prevention of subsequent vertebral fractures in patients treated for osteoporotic vertebral fracture for 12 months: An observational cohort study

“…First, the administration period could be too short to provide a substantial anabolic effect in the TPTD group. A histomorphometric analysis revealed that bone formation significantly increases at least 3 months after TPTD treatment ( Sawakami et al, 2022 ). Second, in previous reports, a higher prevalence of OVF was associated with an increased risk of subsequent OVF ( Hagino et al, 2013 ; Lindsay et al, 2001 ).…”

Effects of Perioperative Teriparatide Treatment on the Hounsfield Unit Values at the Upper Instrumented Vertebra in Adult Spinal Deformity Surgery

“…4 Second, the duration of preoperative TPTD treatment was significantly shorter in the PJF group than in the non-PJF group. Sawakami et al 16 recommended that the optimal duration of preoperative TPTD treatment is 3 months or more in terms of osteoporotic complication rate, clinical score, and bone histomorphometry. Our results further corroborate this, as the average duration of preoperative TPTD treatment was ~3 months in the non-PJF group.…”

Cost-utility Analysis of Neoadjuvant Teriparatide Therapy in Osteopenic Patients Undergoing Adult Spinal Deformity Surgery

“…We chose a regimen of four months based off the authors’ experience with neoadjuvant teriparatide in ASD surgery as well as the current literature on the timing of its anabolic effects. Sawakami et al 24 noted that mineralizing bone surface in iliac crest biopsies, a major indicator of new bone formation, starts to increase after one month of teriparatide treatment and peaks at about four months. In a similar study, Lindsay et al 42 noted that only one month of teriparatide treatment was necessary for significant bone formation.…”

“…We varied the estimates by (±10%). The choice of a four-month treatment regimen was determined based on clinically important minimal time necessary for peak teriparatide anabolic effects 24. The probability of reoperation failure and requiring a third operation was presumed to be 21% (±10%), based on published reports 25…”