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 ... -  《-》

Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones: A Study of Postmenopausal Women with Osteoporosis.

Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Sheth NP ，Smith JR ，Winzenrieth R ，Humbert L ，Wang Y ，Boxberger JI ，Bostrom MP ... -  《-》

Teriparatide and exercise improve bone, skeletal muscle, and fat parameters in ovariectomized and tail-suspended rats.

Sato C ，Miyakoshi N ，Kasukawa Y ，Nozaka K ，Tsuchie H ，Nagahata I ，Yuasa Y ，Abe K ，Saito H ，Shoji R ，Shimada Y ... -  《-》

Bone properties in persons with type 1 diabetes and healthy controls - A cross-sectional study.

The risk of fractures is increased in persons with type 1 diabetes (T1D) and assessment of bone health has been included in the 2024 updated Standards of Care by The American Diabetes Association (ADA). Previous studies have found that in T1D bone metabolism, mineral content, microstructure, and strength diverge from that of persons without diabetes. However, a clear description of a T1D bone phenotype has not yet been established. We investigated bone mechanical properties and microstructure in T1D compared with healthy controls. For the potential future introduction of additional bone measures in the clinical fracture risk assessment, we aimed to assess any potential associations between various measures related to bone indices in subjects with T1D. We studied human bone indices in a clinical cross-sectional setup including 111 persons with early-onset T1D and 37 sex- and age-matched control persons. Participants underwent hip and spine DXA scans for bone mineral density (BMD) of the femoral neck (FN), total hip (TH), and lumbar spine (LS), and TBS evaluation, microindentation of the tibial shaft for Bone Material Strength index (BMSi), and high-resolution periphery quantitative computed tomography (HRpQCT) of the distal radius and tibia for volumetric BMD (vBMD) and structural measures of trabecular and cortical bone. Results are reported as means with (standard deviation) or (95% confidence intervals (CI)), medians with [interquartile range], and differences are reported with (95% CI). The study included 148 persons aged 20 to 75 years with a median age of 43.2 years. The T1D group who had all been diagnosed with T1D before the age of 18 years demonstrated values of HbA1c ranging from 39 to 107 mmol/mol and a median HbA1c of 57 mmol/mol. The BMD did not differ between groups (the mean difference in FN-BMD was 0.026 g/cm2 (-0.026; 0.079), p = 0.319) and the median BMSi was comparable in the two groups (79.2 [73.6; 83.8] in the T1D group compared with 77.9 [70.5, 86.1] in the control group). Total and trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), and trabecular thickness (Tb.Th) of both radius and tibia were lower in participants with T1D. The mean Tb.vBMD at the radius was 143.6 (38.5) mg/cm3 in the T1D group and 171.5 (37.7) mg/cm3 in the control group, p < 0.001. The mean Ct. Thd of the radius was 0.739 mm (0.172) in the T1D group and 0.813 (0.188) in the control group, p = 0.044. Crude linear regressions revealed limited agreement between BMSi and Tb.vBMD (p = 0.010, r2 = 0.040 at the radius and p = 0.008, r2 = 0.040 at the tibia and between BMSi and the estimated failure load (FL) at the tibia (p < 0.001, r2 = 0.090). There were no significant correlations between BMSi and Ct.Th. TBS correlated with Tb.vBMD at the radius (p = 0.008, r2 = 0.044) and the tibia (p = 0.001, r2 = 0.069), and with the estimated FL at the distal tibia (p = 0.038, r2 = 0.026). In this study, we examined the bones of persons with well-controlled, early-onset T1D. Compared with sex- and age-matched healthy control persons, we found reduced total and trabecular vBMD, as well as decreased trabecular and cortical thickness. These results suggest that a debut of T1D before reaching peak bone mass negatively impacts bone microarchitecture. No differences in areal BMD or BMSi were observed. Although the variations in total hip BMD reflect some variation in the vBMD, the reduction in trabecular bone mineral density was not captured by the DXA scan. Consequently, fracture risk may be underestimated when relying on DXA, and further research into fracture risk assessment in T1D is warranted.

Brandt IAG ，Viggers R ，Harsløf T ，Frost M ，Vestergaard P ... -  《-》

Oral daily PTH(1-34) tablets (EB613) in postmenopausal women with low BMD or osteoporosis: a randomized, placebo-controlled, 6-month, phase 2 study.

Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered PTH tablet on serum markers of bone formation (PINP and osteocalcin), bone resorption (crosslinked C-telopeptide [CTX]), BMD, and safety in postmenopausal women with low BMD or osteoporosis. In this 6-mo, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3, and 6 mo and BMD of LS, TH, and FN was measured at 6 mo. Biochemical marker changes were dose dependent with minimal or no effect at the 2 lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 mo after oral PTH initiation (P < .0001), remained elevated through 3 mo, and were back to baseline at 6 mo. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 mo, respectively (both P ≤ .02). At 6 mo, 2.5 mg tablets increased mean BMD vs placebo of the LS by 2.7%, TH by 1.8%, and FN by 2.8% (all P ≤ .01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.

Tripto-Shkolnik L ，Szalat A ，Tsvetov G ，Rouach V ，Sternberg C ，Hoppe A ，Burshtein G ，Galitzer H ，Toledano M ，Harari G ，Santora AC ，Cosman F ... -  《-》