Effects of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate on cortical and trabecular bone of vertebra and proximal femur in postmenopausal women with fragility fracture: Sub-analysis by quantitative computed tomography from the TERABIT study.

PURPOSE: The effects of daily teriparatide (D-PTH, 20 µg/day), weekly high-dose teriparatide (W-PTH, 56.5 µg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT). METHODS: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment. RESULTS: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %). CONCLUSIONS: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur.

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study.

PURPOSE: The effects of daily teriparatide (20 µg) (D-PTH), weekly high-dose teriparatide (56.5 µg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients. METHODS: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months' treatment compared with baseline. RESULTS: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%). CONCLUSIONS: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH.

Effects of monthly intravenous ibandronate on bone mineral density and microstructure in patients with primary osteoporosis after teriparatide treatment: The MONUMENT study.

PURPOSE: To investigate the effects of sequential therapy with monthly intravenous ibandronate on bone mineral density (BMD) and microstructure in patients with primary osteoporosis who received teriparatide treatment. METHODS: Sixty-six patients with primary osteoporosis who had undergone teriparatide treatment for more than 12 months (mean 18.6 months) received sequential therapy with 1 mg/month intravenous ibandronate for 12 months. The patients were evaluated using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound, bone turnover markers, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6 and 12 months after beginning administration. RESULTS: At 12 months after beginning sequential therapy, the bone resorption marker, tartrate-resistant acid phosphatase-5b, decreased by 39.5%, with 82.3% of the patients exhibiting levels within the normal limit. DXA revealed that the BMD of the lumbar spine increased by 3.2%, with 79.0% of the patients exhibiting a response, and 40.3% experiencing an increase in BMD over 5%. HR-pQCT revealed that the cortical thickness of the distal tibia was increased by 2.6%. The cortical area increased by 2.5%, and the buckling ratio (an index of cortical instability) decreased by 2.5%. Most parameters of the trabecular bone showed no significant changes. These changes in the cortical bone were observed in both the distal radius and tibia and appeared beginning 6 months after treatment initiation. CONCLUSIONS: Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment.

Effect of a computer-assisted navigation system on the lag screw placement accuracy of less experienced surgeons.

BACKGROUND: Femoral trochanteric fracture is treated by osteosynthesis using an angle-fixed implant. Lag screw cut-out is a postoperative complication, and a tip-apex distance (TAD) of 20 mm or shorter is recommended to prevent it. The use of a navigation system for lag screw placement has been reported, but the use and non-use of navigation systems by less experienced surgeons has not been assessed. The objective of this study was to retrospectively investigate the usefulness of a navigation system for short femoral nailing. METHODS: The subjects were 101 patients with femoral trochanteric fracture treated by osteosynthesis at our hospital between May 2017 and December 2018 (male, 14; female, 87; mean age, 84.7 years; navigation use group, 55; non-navigation use group, 46). The patients were divided into four groups: groups treated by less experienced surgeons with (Navigation-Young surgeon [NY] group, n = 35) and without (Manual-Young surgeon [MY] group, n = 23) the use of a navigation system; and groups treated by experienced surgeons with (Navigation-Aged surgeon [NA] group, n = 20) and without (Manual-Aged surgeon [MA] group, n = 23) the use of a navigation system. TAD (mm) and operative time (min) were compared. RESULTS: The TAD was significantly longer in the MY group than in the NY group. The percentages of patients with 10-20 mm TAD were as follows: NY group, 94.3%; MY group, 65.2%; NA group, 100%; MA group, 100%. The mean operative time was significantly longer in the NY group than in the MA group, but no significant difference in mean operative time was noted between the NY and MY groups or between the NA and MA groups. CONCLUSIONS: A computer-assisted navigation system improves the accuracy of lag screw placement performed by less experienced operators without increasing the operative time.

Deterioration of bone microstructure by aging and menopause in Japanese healthy women: analysis by HR-pQCT.

INTRODUCTION: Second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61 µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT. MATERIALS AND METHODS: Study participants were 61 healthy Japanese women (31-70 years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed. RESULTS: Trabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength. CONCLUSIONS: Trabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

Analysis of fracture healing process by HR-pQCT in patients with distal radius fracture.

INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe the changes in bone microarchitecture over time in vivo. In this study, the process of fracture healing was analyzed using HR-pQCT in patients with distal radius fracture who underwent osteosynthesis. MATERIALS AND METHODS: A total of 10 fracture sites identified from four patients with a distal radius fracture who underwent internal fixation with a volar locking plate (mean age 68.8 years, all women) were investigated. HR-pQCT was performed within a week (baseline) 4, 12, and 24 weeks after fracture. Rectangular region of interest (ROI) was established in the fracture site, inner callus, and external callus area, and the changes in bone mineral density (BMD) in each region were analyzed. RESULTS: From baseline to 24 weeks post-fracture, the BMD changed from 105.5 (95% CI 98.6-113) to 428.0 (331-554) mgHA/ccm at the fracture site, from 111.0 (104-119) to 375.3 (290-486) mgHA/ccm at the inner callus area, and from 98.5 (91.6-106) to 171.6 (132-222) mgHA/ccm at the external callus area. The BMD increased at the fracture site and inner callus area, but increased only slightly at the external callus area. At 24 weeks post-fracture, the BMD at the fracture site and inner callus area was significantly higher than the external callus area. CONCLUSION: In the healing process of postoperative distal radius fractures, increased BMD at the inner surface of the fracture site was confirmed in all fractures. Bone formation on the endosteal side may be a necessary condition for bone union of distal radius fractures.

The effects of volar locking plates for distal radius fractures on the image quality of high-resolution peripheral quantitative computed tomography.

INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe changes of bone microstructure during fracture healing. However, a method of analyzing the healing process after osteosynthesis has yet to be established due to implant artifacts. The purpose of this study was to investigate the effects of volar locking plates for distal radius fractures on the image quality of HR-pQCT. METHODS: Four different types of plates for distal radius fractures were evaluated. The scan region of HR-pQCT was the center of each plate, not including the screw insertion sites. To assess plate-generated noise, each plate was fixed to the top of a water-filled rubber glove, scanned by HR-pQCT, and the signal-to-noise ratio (SNR) of the region under the plates was calculated. To investigate accuracy, 12 cadaveric radii with and without each plate were scanned by HR-pQCT, and differences between the measured values with and without the plate were evaluated. Differences between the measurements of the entire circumference and of the dorsal third of the radius were also compared. Reproducibility of the in vivo measurement was investigated by repeated scans of 10 patients with distal radius fractures who had undergone surgery with a volar locking plate. RESULTS: The SNR was significantly higher away from the plate than immediately below the plate. Percentage differences of the measurement values between with and without the plate were 1.4%-3.2% for cortical bone mineral density (Ct.BMD) and 7.2%-9.8% for cortical bone thickness (Ct.Th) when the entire circumference was measured. When the dorsal third was measured, they were 0.3%-1.7% for Ct.BMD and 1.8%-2.7% for Ct.Th. The root-mean-square coefficient of variation (RMS%CV) was 1.12% for Ct.BMD and 4.18% for Ct.Th. CONCLUSIONS: The accuracy and reproducibility of cortical bone measurements with a volar locking plate on HR-pQCT were acceptable when the dorsal third of the Ct.BMD was analyzed, and this method would be useful for in vivo analysis of the fracture healing process after osteosynthesis.

Correlation between vertebral bone microstructure and estimated strength in elderly women: An ex-vivo HR-pQCT study of cadaveric spine.

PURPOSE: A vertebral fracture is the most common complication of osteoporosis, and various factors are involved in its occurrence. The purpose of this study was to investigate the role of trabecular and cortical bone microstructure on vertebral strength using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Three female cadaveric spines were investigated (average age: 80.3 years). The whole spine (T1-L4) was scanned by second-generation HR-pQCT at a voxel size of 60.7 µm. Bone microstructure analysis and micro finite element analysis were performed after excluding the upper and lower endplates and posterior elements of a total of 48 vertebrae. Correlations between trabecular and cortical bone microstructure parameters and estimated vertebral strength were analyzed by univariate and multivariate regression models. RESULTS: Cortical thickness (Ct.Th) and trabecular thickness (Tb.Th) were strongly correlated with estimated failure load on univariate analysis (r = 0.89, 0.82). Trabecular volumetric bone mineral density (Tb.vBMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and Ct.Th were correlated with estimated failure load on multivariate regression analysis. CONCLUSIONS: It was suggested that, in addition to trabecular bone (Tb.vBMD, BV/TV, Tb.N), cortical bone (Ct.Th) contributed significantly to vertebral strength in elderly women.