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 TERAB

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). 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. 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 %). 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.

Takahashi R ，Chiba K ，Okazaki N ，Era M ，Yokota K ，Yabe Y ，Kondo C ，Fukuda T ，Fukushima K ，Kono M ，Michikoshi Y ，Yamada S ，Iida T ，Mitsumizo K ，Sato S ，Doi M ，Watanabe K ，Ota S ，Shiraishi K ，Yonekura A ，Osaki M ... -  《-》

Effects of differences in dose and frequency of teriparatide on bone structure in Proximal Femur. - Analysis by DXA-based 3D-modeling (3D-SHAPER Software) -TRIPLE-BONE study (The effects of TeRIParatide preparation on bone mineraL density increase and BON

Trends toward more favorable improvement of the cortical bone parameters by once-weekly (56.5 μg once a week) and twice-weekly teriparatide (28.2 μg twice a week), and that of the trabecular bone parameters by once-daily (1/D) teriparatide (20 μg/day once a day) were shown. To examine the effects of differences in the amount of teriparatide (TPTD) per administration and its dosing frequency on the bone structure in the proximal femur by dual-energy X-ray absorptiometry (DXA)-based 3D-modeling (3D-SHAPER software). This was a multicenter retrospective study. Patients aged 50 years or older with primary osteoporosis who continuously received once-/twice-weekly (1・2/W, n = 60) or 1/D TPTD (n = 14) administration for at least one year were included in the study. Measurement regions included the femoral neck (FN), trochanter (TR), femoral shaft (FS), and total proximal hip (TH). Concurrently, the bone mineral density (BMD) and Trabecular Bone Score (TBS) were measured. The cross-sectional area, cross-sectional moment of inertia, and section modulus in the FS were significantly improved in the 1・2/W TPTD group, as compared to the 1/D TPTD group. However, significant improvement of the cortical thickness and buckling ratio in the FN was observed in the 1/D TPTD group, as compared to the 1・2/W TPTD group. Trabecular BMD values in the FS and TH were significantly increased in the 1/D TPTD group, as compared to the 1・2/W TPTD group, while the cortical BMD values in the TR, FS, and TH were significantly increased in the 1・2/W TPTD group, as compared to the 1/D TPTD group. Trends toward more favorable improvement of the cortical bone by 1・2/W TPTD and that of the trabecular bones by 1/D TPTD were observed.

Takada J ，Okimoto N ，Tsukamoto M ，Akatsuka T ，Takebayashi T ，Iba K ，Ikeda S ... -  《-》

Real-life effects of pharmacological osteoporosis treatments on bone mineral density by quantitative computed tomography.

Monitoring of bone mineral density (BMD) is used to assess pharmacological osteoporosis therapy. This study examined the real-life effects of antiresorptive and osteoanabolic treatments on volumetric BMD (vBMD) of the spine by quantitative computed tomography (QCT). Patients aged ≥ 50 years with a vBMD < 120 mg/ml had ≥ 2 QCT. For analysis of therapy effects, the pharmacological treatment and the duration of each therapy were considered. Identical vertebrae were evaluated in all vBMD measurements for each patient. A linear mixed model with random intercepts was used to estimate the effects of pharmacological treatments on vBMD. A total of 1145 vBMD measurements from 402 patients were analyzed. Considering potential confounders such as sex, age, and prior treatment, a reduction in trabecular vBMD was estimated for oral bisphosphonates (- 1.01 mg/ml per year; p < 0.001), intravenous bisphosphonates (- 0.93 mg/ml per year; p = 0.015) and drug holiday (- 1.58 mg/ml per year; p < 0.001). Teriparatide was estimated to increase trabecular vBMD by 4.27 mg/ml per year (p = 0.018). Patients receiving denosumab showed a statistically non-significant decrease in trabecular vBMD (- 0.44 mg/ml per year; p = 0.099). Compared to non-treated patients, pharmacological therapy had positive effects on trabecular vBMD (1.35 mg/ml; p = 0.001, 1.43 mg/ml; p = 0.004, 1.91 mg/ml; p < 0.001, and 6.63 mg/ml; p < 0.001 per year for oral bisphosphonates, intravenous bisphosphonates, denosumab, and teriparatide, respectively). An increase in trabecular vBMD by QCT was not detected with antiresorptive agents. Patients treated with teriparatide showed increasing trabecular vBMD. Non-treatment led to a larger decrease in trabecular vBMD than pharmacological therapy.

Boehm E ，Sauer C ，Baur-Melnyk A ，Biebl JT ，Harada S ，Wegener B ，Kraft E ，Stahl R ，Feist-Pagenstert I ... -  《-》

HR-pQCT reveals marked trabecular and cortical structural deficits in women with pregnancy and lactation-associated osteoporosis (PLO).

Pregnancy and lactation-associated osteoporosis (PLO) is a rare presentation of early-onset osteoporosis characterized by low trauma and spontaneous fractures during late pregnancy/lactation. Herein, we report areal BMD (aBMD) by DXA and volumetric BMD (vBMD), microarchitecture, and strength at the distal radius and tibia by HR-pQCT in 59 women with PLO-in comparison to both healthy premenopausal controls (n = 28) and premenopausal women with idiopathic osteoporotic fractures not associated with pregnancy/lactation (non-PLO IOP; n = 50). Women with PLO (aged 34 ± 6 yr) had a more severe clinical presentation than non-PLO IOP: 80% had vertebral and 92% had multiple fractures (p<.001). They had lower DXA aBMD at all sites vs Controls (all p<.001) and non-PLO IOP (all p<.05). By HR-pQCT, PLO had deficits in all radial/tibial density and most microarchitecture parameters and lower bone strength than controls (all p<.001). Compared to non-PLO IOP, PLO had lower total and trabecular density at radius and tibia (all p ≤ .01) and significant deficits in trabecular microstructure and cortical thickness at the radius only. We studied PLO subgroups with clinical factors potentially related to bone physiology: Within PLO, women with vertebral fractures had lower spine aBMD and higher tibial cortical porosity but were otherwise structurally similar to the nonvertebral group. Those with prior heparin exposure had larger bone size and trabecular area, and those with renal stones had smaller bone size and lower 1/3 radius aBMD. We also compared groups based on postpartum timing: Recent PLO (n = 25) evaluated ≤12 M postpartum, before expected recovery of pregnancy/lactation bone loss, had significantly lower aBMD than distant PLO (n = 34) evaluated >12 M postpartum. However, radial/tibial HR-pQCT measures did not differ, suggesting pre-existing and/or persistent structural deficits. This structural study increases our mechanistic understanding of the severe bone fragility presentation that characterizes PLO and also highlights areas of potential mechanistic heterogeneity that require additional investigation.

Agarwal S ，El-Najjar D ，Kondapalli A ，Kil N ，Kamanda-Kosseh M ，Bucovsky M ，Colon I ，Lappe JM ，Stubby J ，Recker RR ，Guo XE ，Shane E ，Cohen A ... -  《-》

Effect of bisphosphonate on bone microstructure, mechanical strength in osteoporotic rats by ovariectomy.

Bisphosphonate (BP) can treat osteoporosis and prevent osteoporotic fractures in clinical. However, the effect of BP on microstructure and mechanical properties of cortical and trabecular bone has been taken little attention, separately. In this study, BP was used to intervene in ovariectomized female SD rats. The femoral micro-CT images were used to measure the structural parameters and reconstruct the 3D models in volume of interest. The structural parameters of cortical and trabecular bone were measured, and the mechanical properties were predicted using micro-finite element analysis. There was almost no significant difference in the morphological structure parameters and mechanical properties of cortical bone between normal, ovariectomized (sham-OVX) and BP intervention groups. However, BP could significantly improve bone volume fraction (BV/TV) and trabecular separation (Tb.SP) in inter-femoral condyles (IT) (sham-OVX vs. BP, p < 0.001), and had no significant effect on BV/TV in medial and lateral femoral condyles (MT, LT). Similarly, BPs could significantly affect the effective modulus in IT (sham-OVX vs. BP, p < 0.001), and had no significant difference in MT and LT. In addition, the structural parameters and effective modulus showed a good linear correlation. In a short time, the effects of BP intervention and osteoporosis on cortical bone were not obvious. The effects of BP on trabecular bone in non-main weight-bearing area (IT) were valuable, while for osteoporosis, the main weight-bearing area (MT, LT) may improve the structural quality and mechanical strength of trabecular bone through exercise compensation.

Wang Y ，Wu Z ，Li C ，Ma C ，Chen J ，Wang M ，Gao D ，Wu Y ，Wang H ... -  《BMC MUSCULOSKELETAL DISORDERS》