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 ... -  《-》

Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis.

Leder BZ ，O'Dea LS ，Zanchetta JR ，Kumar P ，Banks K ，McKay K ，Lyttle CR ，Hattersley G ... -  《-》

Differential effects of abaloparatide and teriparatide on hip cortical volumetric BMD by DXA-based 3D modeling.

Winzenrieth R ，Ominsky MS ，Wang Y ，Humbert L ，Weiss RJ ... -  《-》

Abaloparatide increases bone mineral density and bone strength in ovariectomized rabbits with glucocorticoid-induced osteopenia.

Chandler H ，Brooks DJ ，Hattersley G ，Bouxsein ML ，Lanske B ... -  《-》

Abaloparatide Effects on Cortical Volumetric BMD and Estimated Strength Indices of Hip Subregions by 3D-DXA in Women With Postmenopausal Osteoporosis.

In ACTIVE, abaloparatide increased areal BMD (aBMD) of the hip and femoral neck vs teriparatide and placebo in women with osteoporosis. Previously, 3D-processing of dual X-ray absorptiometry (DXA) scans of a subgroup of ACTIVE subjects showed similar increases in trabecular volumetric BMD (Tb.vBMD) and greater increases in cortical vBMD (Ct.vBMD) of the total hip with abaloparatide vs teriparatide. The current analyses from this subgroup describe 2D- and 3D-DXA data for hip subregions. Randomly selected subjects from ACTIVE (n = 250/treatment group) who received 18 mo of placebo, abaloparatide 80 µg, or open-label teriparatide 20 µg by daily subcutaneous injection underwent hip DXA at baseline, and mo 6 and 18 of treatment. Areal BMD of the femoral neck, trochanter, and femoral shaft was determined using standard 2D-DXA and 3D-SHAPER software to retrospectively evaluate changes from baseline in volumetric parameters of these 3 hip subregions, including trabecular and cortical segmentation. Changes in biomechanical parameters cross-sectional moment of inertia (CSMI), section modulus (Z), and buckling ratio were also evaluated. Femoral neck, trochanter, and shaft aBMD increased in the abaloparatide and teriparatide groups at mo 6 and 18 vs placebo, with greater increases for abaloparatide vs teriparatide at the femoral neck at mo 6 and the shaft at mo 6 and 18. All 3 subregions showed similar significant increases in Tb.vBMD with abaloparatide and teriparatide vs placebo, whereas Ct.vBMD of all 3 subregions showed greater increases after 18 mo of abaloparatide vs teriparatide. Biomechanical parameters improved in all subregions with abaloparatide and teriparatide vs placebo, with greater improvements in CSMI and Z of the femoral neck and lower shaft after 6 and 18 mo of abaloparatide vs teriparatide. Differential femoral neck and shaft Ct.vBMD responses may explain the greater increases in CSMI and Z of those subregions with abaloparatide vs teriparatide.

Winzenrieth R ，Humbert L ，Boxberger JI ，Weiss RJ ，Wang Y ，Kostenuik P ... -  《-》