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

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  • 1 Department of Orthopaedic Surgery, Niigata City General Hospital, Niigata, Japan;
  • | 2 Department of Orthopaedic Surgery, Niigata University Medical and Dental Hospital, Niigata, Japan;
  • | 3 Niigata Spine Surgery Center, Niigata, Japan;
  • | 4 Niigata Bone Science Institute, Niigata, Japan; and
  • | 5 Department of Orthopaedic Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
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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.

ABBREVIATIONS

BFR = bone formation rate; BMD = bone mineral density; BP = bisphosphonate; BS = bone surface; BV = bone volume; DEXA = dual-energy x-ray absorptiometry; ES = eroded surface; MAR = mineral apposition rate; MS = mineralizing surface; NTC = no neoadjuvant therapy; Ob.S = osteoblast surface; Oc.S = osteoclast surface; ODI = Oswestry Disability Index; OS = osteoid surface; O.Th = osteoid thickness; OV = osteoid volume; P1NP = procollagen type I N-terminal propeptide; Tb.N = trabecular number; Tb.Th = trabecular thickness; Tb.Sp = trabecular separation; TPTD = teriparatide; TV = tissue volume.

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