Sweep imaging with Fourier transform as a tool with MRI for evaluating the effect of teriparatide on cortical bone formation in an ovariectomized rat model

Background Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone quality. However, the effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating bound water of cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the consequences of the effect of TPTD on cortical bone formation using SWIFT. Methods Twelve-week-old female Sprague-Dawley rats (n = 36) were reared after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate the bone formation rate by bone histomorphometry. Measurements were compared using the Mann-Whitney U-test, and a P-value of < 0.05 was considered significant. Results PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate assessed by histomorphometry was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (P = 0.028, 1.98 ± 0.33 vs. 0.09 ± 0.05 μm3/μm2/day). Conclusions SWIFT could detect increased signals of bound water, reflecting the effect of TPTD on the cortical bone. The signal detected by SWIFT reflects a marked increase in the cortical bone formation rate.

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

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.

Sweep Imaging with Fourier Transform as a Tool for Evaluating the Effect of Teriparatide on Cortical Bone Turnover in an Ovariectomized Rat Model

Background: Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone turnover. However, the specific effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the effects of TPTD on cortical bone turnover using SWIFT in rats. Methods: Twelve-week-old female Sprague-Dawley rats (n=36) were reared for 12 weeks after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were extracted and evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate for the bone formation rate by bone histomorphometry . Measurements were compared using the Mann-Whitney U-test, and a P-value of <0.05 was considered significant. Results: PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (1.98±0.33 vs. 0.09±0.05 μm3/μm2/day).Conclusions: The marked increase of the bone formation rate in the cortical bone by TPTD could be measured using SWIFT. SWIFT could be an effective tool for evaluating the effects of TPTD on cortical bone turnover as images.

Supplementation of Morin Restores the Altered Bone Histomorphometry in Hyperglycemic Rodents via Regulation of Insulin/IGF-1 Signaling

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin’s protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.