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.

Precision of 3D Registration Analysis for Longitudinal Study of Second-Generation HR-pQCT.

OBJECTIVE: The objective of this research was to develop 3D registration analysis method in longitudinal studies of high-resolution peripheral quantitative computed tomography (HR-pQCT), to analyze ranges of bone microstructure parameters in addition to standard parameters, and to test the precision of these measurements. METHODS: Scans of HR-pQCT and analysis of bone microstructure were performed at 3 times in 15 subjects. The 3 images were matched 3-dimensionally, and bone microstructures were analyzed in the common region. In addition to standard measurement parameters of geometry, bone mineral density (BMD), trabecular bone, and cortical bone, parameters showing plate to rod-like structure, connectivity, cavity formation of trabecular bone, and bending stability of cortical bone were also measured. Precision was evaluated with the root mean square percent coefficient variance (RMS%CV). RESULTS: RMS%CV was 0.1%-1.3% for geometry, 0.6%-1.9% for BMD, 0.8%-3.3% for trabecular bone, 2.1%-9.8% for additionally measured trabecular bone, 1.0%-3.4% for cortical bone excluding Ct.Po, 6.0%-6.1% for Ct.Po, and 0.8%-1.5% for additionally measured cortical bone. Precision was higher for 3D registration than for 2D registration in geometry, BV/TV, and Ct.Po. CONCLUSIONS: 3D registration analysis of a range of bone microstructural parameters in longitudinal analysis of HR-pQCT showed good precision, offering potential for contributing to future research on osteoporosis and bone metabolic diseases.

Precision of Second-Generation High-Resolution Peripheral Quantitative Computed Tomography: Intra- and Intertester Reproducibilities and Factors Involved in the Reproducibility of Cortical Porosity.

High-resolution peripheral quantitative computed tomography (HR-pQCT) was upgraded to a second generation in 2014 with higher spatial resolution, faster scan time, and a different measurement algorithm. The purpose of this study was to investigate the precision of the second-generation HR-pQCT. The distal radius and tibia of 15 healthy men and women (age range of 20-74 yr, 8 men and 7 women) were scanned by second-generation HR-pQCT, and their geometry, bone mineral density (BMD), and the microstructure of trabecular and cortical bones were evaluated. Scans and measurements were performed by tester 1 at baseline and at 1 and 4 wk to evaluate intratester reproducibility, and by testers 2 and 3 one time each to evaluate intertester reproducibility. Reproducibility was evaluated by root mean square percent coefficient of variance (RMS%CV). Factors involved in the reproducibility of cortical porosity (Ct.Po) were also investigated. The ranges of RMS%CV were 0.2%-2.5% for geometry, 0.6%-1.7% for BMD, 0.7%-2.4% for trabecular bone, and 1.1%-1.3% for cortical thickness, showing excellent reproducibility. The range of RMS%CV for Ct.Po was 11.0%-13.3%, relatively higher than those for the other parameters. There was no apparent difference between intra- and intertester reproducibilities. There was no clear correlation between the percent coefficient of variance of Ct.Po and the subjects' background characteristics, motion artifact, and cortical bone structure. The reproducibility of the second-generation HR-pQCT was excellent in geometry, BMD, trabecular bone, and cortical thickness, with no apparent difference between intra- and intertester reproducibilities. Compared with the first-generation HR-pQCT, the reproducibility of trabecular bone was improved. The reproducibility of Ct.Po was insufficient and needed to be improved, and factors that influence its reproducibility were not clear.