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.

Bone microstructure in healthy men measured by HR-pQCT: Age-related changes and their relationships with DXA parameters and biochemical markers.

OBJECTIVE: The primary purpose of this cross-sectional study was to investigate the characteristics of age-related changes in bone microstructure on high-resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) on dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers in men. The secondary purpose of this study was to examine how bone microstructure is related to aBMD and biochemical markers. METHODS: The subjects were 128 healthy Japanese men (20-97 years old). Bone microstructure was measured in the distal radius and tibia using second-generation HR-pQCT; aBMD in the proximal femur and lumbar spine was measured with DXA; and tartrate-resistant acid phosphatase-5b (TRACP-5b), type I procollagen-N-propeptide (P1NP), 25(OH) vitamin D, and pentosidine concentrations were measured by blood tests. RESULTS: In trabecular bone, the trabecular volumetric BMD (Tb.vBMD) and trabecular number (Tb.N) were lower with age (r = -0.23, -0.35) (r = -0.36,-0.33), and trabecular separation (Tb.Sp) and the star volume of marrow space (V*ms) were higher with age (r = 0.29, 0.41) (r = 0.34, 0.38) in both the radius and tibia. In cortical bone, cortical volumetric BMD (Ct.vBMD) was lower with age (r = -0.25, -0.52), and cortical porosity (Ct.Po) was higher with age (r = 0.67, 0.62) in both the radius and tibia. In the tibia, cortical thickness (Ct.Th) and cortical area (Ct.Ar) were lower with age (r = -0.40) (r = -0.43), whereas, in the radius, they were maintained, and periosteal perimeter (Ct.Pm) was higher with age (r = 0.35). aBMD in the proximal femur and P1NP were lower, and pentosidine was higher with increased age, whereas aBMD in the lumbar spine, TRACP-5b, and 25(OH) vitamin D had no relationships with age. DXA and HR-pQCT showed strong correlations particularly with femoral aBMD and tibial Tb.vBMD and Ct.Ar (r = 0.61) (r = 0.61), whereas no DXA parameters were related with Ct.Po. In correlations between biochemical markers and HR-pQCT, TRACP-5b and total P1NP were negatively correlated with Ct.vBMD (r = -0.31) (r = -0.35), but almost no other correlations were seen. CONCLUSIONS: Age-related changes of the bone microstructure in men were characterized by decreases in trabecular and cortical vBMD associated with decreased trabecular number, cavitation of the trabecular structure, and increased cortical porosity. Femoral aBMD was strongly related to bone microstructure in the tibia, whereas both lumbar aBMD and femoral aBMD were not related to Ct.Po, and biochemical markers showed almost no relationships with bone microstructure.

Differences in bone mineral density and morphometry measurements by fixed versus relative offset methods in high-resolution peripheral quantitative computed tomography.

INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT), which enables in vivo analysis of bone morphometry, is widely used in osteoporosis research. The scan position is usually determined by the fixed offset method; however, there are concerns that the scan position can become relatively proximal if limb length is short. The present study compared bone mineral density and morphometry measured using the fixed and relative offset methods, in which the scan position is determined based on the lengths of the forearm and lower leg, and investigated factors responsible for measurement differences between the two methods. METHODS: A total of 150 healthy Japanese subjects, comprising 75 men and 75 women, with a mean age of 45.1 years, were enrolled in this study. The distal radius and tibia were scanned using the fixed and relative offset methods; the fixed offset method involved scanning the radius and tibia at 9 mm and 22 mm, respectively, proximal to their distal articular surfaces. By contrast, the relative offset method entailed scanning the radius at 4% of the forearm length and the tibia at 7.3% of the lower leg length, proximal to their respective distal articular surfaces. The percent overlap between the scan positions of the two methods was measured using the scout views. Measurement values obtained with the two methods were compared. The correlation between the differences in the values among the two methods and forearm length, lower leg length, and body height was examined. RESULTS: The subjects had a mean height of 164.3 ± 14.3 cm, mean forearm length of 252.9 ± 17.3 mm, and mean lower leg length of 346.7 ± 22.3 mm. The mean percent overlap was 85.0 ± 9.1% (59.2-99.6%) for the radius and 79.8 ± 12.5% (48.3-99.8%) for the tibia. Fixed offset scanning yielded higher total volumetric bone mineral density (Tt.vBMD) and cortical vBMD (Ct.vBMD) and greater cortical thickness (Ct.Th) (all p < 0.001). The differences between the two methods in terms of Tt.vBMD, Ct.vBMD and Ct.Th were significantly greater with shorter forearm length, lower leg length, and body height (radius: 0.51 < |r| < 0.63, tibia: 0.61 < |r| < 0.95). CONCLUSION: Measurements of bone mineral density and morphometry obtained using the fixed offset method differed from those obtained using the relative offset method, which takes body size into account. Shorter body height, forearm length, and lower leg length were found to correlate with greater measurement differences. In populations with smaller stature, use of the fixed offset method results in relatively proximal images; thus, caution should be exercised when comparing groups of different height.

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.