Osteoporosis at the time of total hip arthroplasty (THA) is associated with suboptimal primary and secondary hip stem fixation, stem loosening, and an increased risk of intraoperative and postoperative periprosthetic fractures1,2. Additionally, adverse effects of low hip bone mineral density (BMD) can be compounded by postoperative bone loss around the femoral stem3 and subsequent peri-implant bone loss4–6. Given this elevated risk of complications following THA, bone health optimization, a paradigm that preoperatively evaluates and, when appropriate, preoperatively treats osteoporosis2,7,8, is an attractive and intuitive step9. Bone health optimization is now advocated by several orthopaedic-related organizations, including the International Society for Clinical Densitometry (ISCD)10, American Orthopaedic Association (AOA)8, and the Bone Health & Osteoporosis Foundation (BHOF), formerly the National Osteoporosis Foundation (NOF)7. Treatment options for bone health optimization include antiresorptive agents (e.g., bisphosphonates or denosumab) that reduce bone loss by inhibiting bone remodeling, and osteoanabolic agents, which increase BMD by stimulating bone formation8,9.

Abaloparatide, a novel osteoanabolic synthetic parathyroid hormone receptor agonist and candidate agent for bone health optimization, stimulates bone formation with lower increases in bone resorption, resulting in increased BMD at multiple skeletal sites, including the hip11. As an anabolic agent, the mechanism of action of the promotion of bone formation, differs from the antiresorption mechanism of agents including bisphosphonates, results in more rapid accrual of BMD, and elevates the potential for abaloparatide use in bone health optimization9. Dual x-ray absorptiometry (DXA) data from the Phase-3 Abaloparatide for the Treatment of Men with Osteoporosis (ATOM) trial (NCT03512262) demonstrated significantly increased areal BMD of the femoral neck and lumbar spine within 3 months of treatment compared with placebo12. The Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) study (NCT01343004) in postmenopausal women with osteoporosis also showed increased areal BMD compared with placebo and open-label teriparatide after 6 months and 18 months of treatment11,13,14. In the ACTIVE study, abaloparatide also reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures compared with placebo, and prespecified exploratory analyses showed a lower risk of major osteoporotic fractures with abaloparatide compared with teriparatide13. In further post hoc analysis specific to the hip, the ACTIVE data showed that abaloparatide increased cortical volumetric BMD of the trochanter, femoral shaft, and femoral neck compared with teriparatide or placebo. Additionally, abaloparatide treatment resulted in greater improvements in biomechanical parameters of the femoral shaft compared with teriparatide or placebo after 6 months15,16.

Further investigation of abaloparatide at the hip is warranted to better understand its potential in the setting of bone health optimization and to identify the effects of abaloparatide in femoral regions specifically relevant to THA. Gruen et al. defined 7 hip regions around femoral stems, commonly known as Gruen zones 1 through 7 (Fig. 1), and described their relationships with various modes of implant loosening and failure17. Gruen zones have also been applied to femora without implants to generate finite element models for predicting osteoporotic hip fracture risk18. Gruen zone 1, the trabecula-rich proximolateral region that includes the greater trochanter, has the lowest BMD around the time of THA and experiences substantial BMD loss after THA3,5,19–23. Gruen zone 7, the proximomedial region that includes the calcar and lesser trochanter, also has comparatively low BMD around the time of the THA18,19,22 and is highly susceptible to postoperative BMD loss3,5,6,20,21,23,24. Low BMD in zone 7 is associated with loose femoral implants25 and is a main location for intraoperative periprosthetic fractures, which are more common in women and patients >65 years of age26.

Fig. 1:

Virtual implant placement (Fig. 1-A) and delineation of the Gruen zones (Fig. 1-B). In Figure 1-B, plane 1 was fitted through the lesser trochanter perpendicular to the shaft axis. Plane 2 was orthogonal to the cross-product of the shaft axis and the sagittal axis. Plane 3 bisected the distance from the stem tip to the first plane drawn. aThe zone 2 height is 53% of the theoretical zone 2 height.

The objective of the current post hoc analysis of the ACTIVE trial is to evaluate responses to abaloparatide compared with placebo in 3-dimensional (3D) hip regions corresponding to Gruen zones by leveraging virtual placement of a femoral stem implanted without cement. We hypothesized that the Gruen zones captured would show greater BMD increases after 6 and 18 months of abaloparatide treatment compared with placebo. Data supporting this hypothesis may indicate strategically located bone accrual for patients with a high fracture risk and osteoporosis who are current or future candidates for elective THA.

Materials and Methods Study Design and Population

The ACTIVE trial was a Phase-3, double-blinded, placebo-controlled study with an open-label teriparatide comparator arm that enrolled 2,463 women with postmenopausal osteoporosis based on various BMD and clinical criteria for high fracture risk13. The current post hoc analyses are based on a subset of 500 ACTIVE trial patients (250 who were treated with abaloparatide and 250 who received placebo) who were randomly selected, with stratification by study site and race/ethnicity15. The hip scans underwent 3D-DXA modeling (3D-SHAPER, version 2.10.1; 3D-Shaper Medical), as described previously27, generating 3D patient-specific reconstructions from hip DXA scans for further analyses. The 3D-DXA uses a statistical shape and density model of a proximal femur built from a database of quantitative computed tomography images, which is registered onto the DXA scan to estimate a patient-specific 3D femoral shape and volumetric density distribution28. Cortical bone is segmented by fitting a function of the cortex location, cortical volumetric BMD, cortical thickness, imaging blur, and density of surrounding tissues to the density profile calculated from the normal vector at each vertex of the proximal femoral surface mesh, as previously described29. Cortical surface BMD is calculated as the product of cortical thickness and cortical volumetric BMD. Trabecular volumetric BMD is calculated as the mean bone density inside the endocortical surface, and integral volumetric BMD is calculated as the mean bone density of the cortical plus trabecular compartments28.

The ACTIVE trial was approved by the ethics committee at every participating institution and was conducted according to the recommendations of Good Clinical Practice and the Declaration of Helsinki. All patients provided written informed consent to participate13.

Virtual Femoral Stem Implant Placement and Gruen Zone Analyses

A virtual model of a flat-wedge, tapered, cementless Stryker Accolade II hip stem was optimally sized and virtually positioned within each 3D femoral reconstruction using in-house MATLAB (MathWorks) code. A size-4 implant with a high-offset 127° neck angle, 35-mm neck length, 105-mm stem length, and 42-mm offset was selected as the model template. This implant was chosen because, when positioned within the mean 3D-DXA statistical femoral model, it provided maximal contact surface between the implant and a virtual surface located 1 mm inside the endocortical surface, and the closest alignment of the implant head with the formal head center. To adapt the stem model to each patient-specific reconstruction and optimize femoral fit, rigid and nonrigid thin plate spline transformations between the mean 3D-DXA statistical femoral endocortical shape and each patient-specific endocortical shape were calculated. Those transformations were then applied to the implant shape for each patient, thus changing the implant from the starting geometry and position in order to ensure a patient-specific, optimally sized implant and a reproducible fit between patients.

After virtual placement of the optimized implant, the proximal femoral model was virtually resected superiorly to simulate surgical resection for stem implantation (Fig. 1-A); 1 cut passed obliquely through the base of the implant neck, and the other cut passed transversely through the upper corner of the base of the implant neck parallel with the implant shaft axis. Gruen zones were then delineated on the basis of 3 planes (Fig. 1-B). Plane 1 passes through the center of the lesser trochanter and is perpendicular to the shaft axis, plane 2 passes through the shaft axis and is orthogonal to the cross-product of the shaft axis and the sagittal axis, and plane 3 is perpendicular to the shaft axis and is positioned 1 cm below the base of the lesser trochanter. Ultimately, Gruen zones 1 and 7 were fully captured, whereas 53% of zones 2 and 6 were captured on the basis of the maximal distance across the fields of view for all of the original DXA scans. Cortical surface BMD, cortical volumetric BMD, trabecular volumetric BMD, integral volumetric BMD, and cortical thickness were calculated for the 4 Gruen zones. To further characterize bone at the virtual implant surface, changes in volumetric BMD were calculated and visualized in a region extending 5 mm into the bone from the implant surface in all directions.

Statistical Analysis

Comparisons of the abaloparatide and placebo groups were made using the change from baseline, with p values derived from contrast tests based on a mixed-effect, repeated-measures model that adjusted for body mass index, age, value at baseline, DXA scanner model, treatment group, visit, and treatment group-visit interaction. The 3D spatial distribution of the mean volumetric BMD changes between baseline and each follow-up time point was evaluated. All inferential tests were 2-tailed, and significance was set at p < 0.05. Statistical comparisons were performed with SAS version 9.4 (SAS Institute).

Results

Prior to treatment, all 3D-DXA parameters in the 4 Gruen zones had similar baseline values in the abaloparatide and placebo groups (Table I). Among the 4 Gruen zones analyzed, zone 1 had the lowest baseline integral volumetric BMD and cortical thickness, followed by zone 7. Zone 1 also had the lowest baseline cortical surface BMD, followed by zone 7. Zones 1 and 7 had the highest baseline trabecular volumetric BMD, and zones 2 and 6 had the highest cortical thickness.

TABLE I - Baseline 3D-DXA Parameter Values for the Abaloparatide and Placebo Groups Absolute Values at Baseline* Abaloparatide Group (N = 250) Placebo Group (N = 250) Integral volumetric BMD†(mg/cm 3 )  Gruen zone 1 240.36 ± 40.69 242.15 ± 40.26  Gruen zone 7 301.71 ± 53.58 304.26 ± 53.27 Trabecular volumetric BMD†(mg/cm 3 )  Gruen zone 1 113.56 ± 31.78 115.64 ± 30.28  Gruen zone 7 116.47 ± 36.74 118.38 ± 33.49 Cortical volumetric BMD (mg/cm 3 )  Gruen zone 1 789.18 ± 73.48 790.74 ± 79.81  Gruen zone 2 779.22 ± 87.87 783.13 ± 95.96  Gruen zone 6 786.45 ± 94.65 790.44 ± 94.28  Gruen zone 7 704.45 ± 85.51 706.79 ± 91.37 Cortical thickness (mm)  Gruen zone 1 1.28 ± 0.13 1.28 ± 0.12  Gruen zone 2 3.23 ± 0.35 3.22 ± 0.35  Gruen zone 6 3.53 ± 0.36 3.52 ± 0.34  Gruen zone 7 2.12 ± 0.17 2.11 ± 0.19 Cortical surface BMD‡(mg/cm 2 )  Gruen zone 1 84.48 ± 13.55 84.44 ± 13.26  Gruen zone 2 251.13 ± 44.55 250.24 ± 43.85  Gruen zone 6 276.99 ± 46.25 276.73 ± 44.81  Gruen zone 7 156.21 ± 21.83 156.07 ± 23.66

*The values are given as the mean and the standard deviation at baseline (month 0).

†Integral and trabecular volumetric BMD baseline values for Gruen zones 2 and 6 are not listed due to the minimal amount of trabecular bone remaining postoperatively.

‡Surface BMD = cortical volumetric BMD × cortical thickness.

Abaloparatide treatment significantly increased integral volumetric BMD compared with placebo in all 4 Gruen zones after 6 and 18 months (p < 0.005 for all) (Figs. 2-A through 2-D), with zones 1 and 7 showing the largest gains (both p < 0.0001 compared with placebo). Trabecular volumetric BMD in zones 1 and 7 increased significantly with abaloparatide compared with placebo at months 6 and 18 (p < 0.0001 for all) (Table II). The change in trabecular volumetric BMD in zones 2 and 6 could not be reliably evaluated, as most of the trabecular bone in those regions was virtually removed during implant fitting, and was thus not reported. The increase from baseline in cortical volumetric BMD was significantly greater with abaloparatide compared with placebo at month 18 in all zones (p < 0.01 for all) (Table II). Cortical thickness increased significantly from baseline with abaloparatide treatment compared with placebo in zones 1, 6, and 7 at month 6 (p < 0.01 for all), and in all zones at month 18 (p < 0.0005 for all) (Table II). Cortical surface BMD increased significantly from baseline with abaloparatide treatment compared with placebo in zones 1, 6, and 7 at month 6 (p < 0.005 for all) and in all zones at month 18 (p < 0.0001 for all) (Table II). The spatial distribution of mean changes from baseline in cortical surface BMD is illustrated in Figure 3. The placebo group had minimal changes in cortical surface BMD at months 6 and 18, whereas the abaloparatide group showed increases in cortical surface BMD across most of the proximal femoral surface by month 6, with further increases at month 18 involving nearly the entire cortical surface.

Fig. 2:

Figs. 2-A through 2-D Percent change from baseline in integral volumetric BMD (vBMD [cortical + trabecular BMD]) of the 4 analyzed Gruen zones (Gruen zone 1 [Fig. 2-A], Gruen zone 2 [Fig. 2-B], Gruen zone 6 [Fig. 2-C], and Gruen zone 7 [Fig. 2-D]) after 6 and 18 months of abaloparatide (ABL) or placebo (PBO). The values are shown as the group mean and the 95% confidence interval. **P < 0.005. ***P < 0.0001.

TABLE II - Percent Change from Baseline After 6 and 18 Months of Abaloparatide Compared with Placebo 6 Months 18 Months Abaloparatide* (N = 250) Placebo* (N = 250) P Value Abaloparatide* (N = 250) Placebo* (N = 250) P Value Trabecular volumetric BMD†  Gruen zone 1 7.45 (6.20 to 8.69) 0.86 (−0.13 to 1.84) <0.0001 10.59 (8.97 to 12.21) −0.49 (−1.63 to 0.65) <0.0001  Gruen zone 7 8.45 (6.49 to 10.42) 1.01 (−0.18 to 2.21) <0.0001 12.23 (9.81 to 14.65) −0.34 (−1.65 to 0.96) <0.0001 Cortical volumetric BMD  Gruen zone 1 0.19 (−0.42 to 0.81) 0.47 (−0.19 to 1.12) 0.4687 1.49 (0.74 to 2.23) 0.11 (−0.56 to 0.77) 0.0067  Gruen zone 2 0.44 (−0.21 to 1.09) 0.12 (−0.56 to 0.80) 0.5810 1.66 (0.94 to 2.38) −0.26 (−0.93 to 0.41) 0.0001  Gruen zone 6 0.78 (0.14 to 1.43) 0.24 (−0.31 to 0.80) 0.2413 1.79 (1.13 to 2.45) −0.27 (−0.86 to 0.32) <0.0001  Gruen zone 7 1.32 (0.49 to 2.16) 0.60 (−0.21 to 1.41) 0.2716 2.45 (1.58 to 3.31) 0.05 (−0.89 to 0.98) 0.0002 Cortical thickness  Gruen zone 1 1.10 (0.66 to 1.55) 0.15 (−0.27 to 0.58) 0.0030 1.60 (1.03 to 2.16) 0.13 (−0.38 to 0.65) 0.0002  Gruen zone 2 0.54 (0.03 to 1.04) 0.18 (−0.22 to 0.58) 0.2909 1.50 (0.94 to 2.05) 0.07 (−0.44 to 0.58) 0.0002  Gruen zone 6 0.82 (0.42 to 1.22) −0.27 (−0.62 to 0.09) <0.0001 2.22 (1.72 to 2.73) −0.24 (−0.62 to 0.14) <0.0001  Gruen zone 7 0.76 (0.42 to 1.10) −0.04 (−0.35 to 0.27) 0.0009 1.79 (1.37 to 2.20) 0.16 (−0.17 to 0.49) <0.0001 Cortical surface BMD‡  Gruen zone 1 1.73 (1.09 to 2.38) 0.41 (−0.20 to 1.02) 0.0035 3.25 (2.46 to 4.03) −0.06 (−0.78 to 0.65) <0.0001  Gruen zone 2 1.00 (0.30 to 1.70) 0.42 (−0.13 to 0.98) 0.2081 2.94 (2.19 to 3.69) −0.16 (−0.81 to 0.49) <0.0001  Gruen zone 6 1.30 (0.70 to 1.90) −0.09 (−0.58 to 0.41) 0.0005 3.72 (3.03 to 4.41) −0.50 (−1.06 to 0.05) <0.0001  Gruen zone 7 1.24 (0.76 to 1.71) 0.16 (−0.23 to 0.55) 0.0007 3.29 (2.74 to 3.84) −0.08 (−0.52 to 0.36) <0.0001

*The values for the change from baseline are given as the mean percentage, with the 95% CI in parentheses.

†Trabecular volumetric BMD change from baseline values for Gruen zones 2 and 6 are not reported because of the minimal amount of trabecular bone remaining postoperatively.

‡Surface BMD = cortical volumetric BMD × cortical thickness.

Fig. 3:

Spatial distribution of mean percentage changes in cortical surface BMD after 6 and 18 months of abaloparatide or placebo. Regions exhibiting increased surface BMD are shaded blue and green, and decreases in surface BMD are depicted in yellow and red. Changes are projected onto the mean cortical shell of the baseline 3D-DXA models.

Figure 4 depicts mean volumetric BMD changes in the osseous envelope residing within 5 mm of the simulated implant surface. Minimal volumetric BMD changes were observed with placebo at month 6, but, at month 18, reduction in volumetric BMD by up to approximately 10 mg/cm3 was seen at the medial implant surface. At month 6, the abaloparatide group showed increased volumetric BMD along most implant surfaces, generally by 5 to 10 mg/cm3. Further increases in volumetric BMD were observed after 18 months of abaloparatide, particularly along the medial (calcar-adjacent) surface, with volumetric BMD gains in the 10 to 20-mg/cm3 range. Finally, a 2-dimensional visualization of changes in volumetric BMD was created in 3 planes: a frontal plane, an intertrochanteric plane, and an axial plane through the shaft of the femur (Fig. 5). Positive changes in volumetric BMD with abaloparatide treatment were evident at the periosteal and endosteal cortical surfaces and additionally in areas rich in trabecular bone at 6 and 18 months, in contrast to modest declines noted in the placebo group. Collectively, these colorimetric qualitative analyses support the quantitative Gruen zone analysis and provide insight into the 3D nature of the BMD changes within each zone.

Fig. 4:

Spatial distribution of the mean changes in volumetric BMD within 5 mm of the implant, projected onto the implant surface, after 6 or 18 months of abaloparatide or placebo. Regions exhibiting increased surface BMD are shaded blue and green, and decreases in surface BMD are depicted in yellow and red.

Fig. 5:

Comparison of distribution of volumetric BMD (vBMD) changes for frontal, intertrochanteric, and shaft planes 18 months after abaloparatide treatment or placebo.

Discussion

This study evaluated the effects of 6 or 18 months of systemic abaloparatide treatment compared with placebo on changes in the proximal femur of postmenopausal women with osteoporosis from the ACTIVE trial, with a focus on subregions relevant to THA. All 4 Gruen zones evaluated (1, 2, 6, and 7) showed early and progressive increases in integral volumetric BMD with abaloparatide treatment. Zones 1 and 7, which have the lowest integral volumetric BMD and cortical thickness at baseline, also showed significant increases in cortical thickness, cortical surface BMD, and trabecular volumetric BMD, and a numerical increase in cortical volumetric BMD with 6 months of abaloparatide treatment. These findings may have relevance for patients with osteoporosis who are current or future candidates for elective THA. Although the results do not reflect physical interactions between abaloparatide-related bone changes and an actual implant, they may suggest that abaloparatide has a utility for preoperative bone health optimization in candidates for THA with poor bone quality.

Osteoporosis is relatively common among older individuals preparing for THA30, and many surgeons consider low BMD to be an important factor to include when determining operative strategy31. These are among the rationales behind recommendations to implement DXA screening prior to THA7,8. Cemented femoral components are often used to improve fixation in older individuals with osteoporosis32. However, cement increases operating time and may complicate implant retrieval if revision becomes necessary33, making preoperative normalization of BMD a potentially attractive strategy for prolonging the opportunity for a cementless approach. For patients with osteoporosis who are preparing for elective orthopaedic surgery, a time frame of 2 to 6 months has been suggested as a reasonable duration of preoperative osteoporosis therapy34. The current results show that 6 months of abaloparatide treatment significantly improved BMD in all 4 analyzed Gruen zones. Other trials in men and postmenopausal women with osteoporosis that included earlier DXA assessments showed that abaloparatide significantly increased total hip BMD within 3 months12,35. Further analysis would be fruitful to determine the relevance of early BMD changes to strength-related parameters, which may relate to prevention of implant failure.

Preoperative or perioperative treatment with an osteoanabolic agent such as abaloparatide may support implant longevity through mechanisms beyond the accrual of BMD within the defined Gruen zones of this study. Abaloparatide has been shown to improve the fixation of titanium implants placed in the trabecula-rich proximal tibia of rodents36. Further, dynamic bone histomorphometry data from postmenopausal women with osteoporosis and from animals with low BMD have indicated that abaloparatide robustly stimulates endocortical bone formation37–39, an effect that could favor the osseointegration of endocortically placed implants. Nonhuman primate data have shown that increased endocortical bone formation with abaloparatide is accompanied by a reduced femoral endocortical perimeter39, an effect that may favor the primary fixation of press-fit implants and potentially reduce the risk of intraoperative fractures. Abaloparatide also increases periosteal bone formation in postmenopausal women with osteoporosis37, and animal studies have shown that increased periosteal bone formation with abaloparatide is associated with periosteal expansion, increased cortical thickness, and greater femoral bending strength40. Previous 3D-DXA analyses from the ACTIVE trial have also shown that 6 and 18 months of abaloparatide treatment have biomechanically favorable effects on structural properties of the upper femoral shaft, including the cross-sectional moment of inertia, section modulus, and buckling ratio15. Ultimately, additional work is needed to evaluate the full potential benefits of bone health optimization with abaloparatide. Initial insights into the effects of abaloparatide therapy on peri-implant BMD changes and complications may come from an ongoing clinical trial of men and postmenopausal women with osteoporosis who are scheduled for total knee arthroplasty, with 18 months of abaloparatide treatment starting 3 months preoperatively (ClinicalTrials.gov: NCT04167163).

This current study had several limitations. ACTIVE trial participants were not selected for conditions that warrant THA, and such patients may show different responses to abaloparatide based on hip degenerative changes, pain-related stress-shielding, and other factors. Comparisons between medications were not possible because the current analyses did not include ACTIVE trial patients treated with open-label teriparatide, although extensive 3D-DXA data from that group can be found in other publications15,16. Furthermore, Gruen zones are based on femoral implant specifications, and different implants than the current model may yield different results. The lack of data on Gruen zones 3 to 5 in the current study was an unavoidable technical limitation due to a limited DXA field of view. However, zones 3 to 5 generally have the highest BMD in nonimplanted and recently implanted femora18,19,24 and also exhibit less postoperative BMD loss relative to other Gruen zones3,20,21,23,24. Thus, the most vital zones were fully or partially captured. Finally, this study should be looked at as hypothesis-generating, and clinical confirmation of the modeled and theoretical benefits of increased BMD around an implanted stem with abaloparatide use should be sought.

In summary, the current findings provide further evidence of favorable effects of abaloparatide on the hip in patients with osteoporosis. An early and persistent increase in integral volumetric BMD and cortical thickness of the 2 virtual Gruen zones with the lowest baseline BMD, and the greatest postoperative BMD loss in patients undergoing THA, may indicate that abaloparatide treatment can result in strategically localized BMD gains that are potentially beneficial for the longevity of a future implant. Further studies are warranted to evaluate the effects of preoperative, perioperative, and postoperative abaloparatide therapy on implant-supporting bone regions in patients with osteoporosis who are undergoing THA.

References 1. Aro HT, Alm JJ, Moritz N, Mäkinen TJ, Lankinen P. Low BMD affects initial stability and delays stem osseointegration in cementless total hip arthroplasty in women: a 2-year RSA study of 39 patients. Acta Orthop. 2012 Apr;83(2):107-14. 2. Liu C, Brinkmann E, Chou SH, Tejada Arias K, Cooper L, Javedan H, Iorio R, Chen AF. Team approach: preoperative management of metabolic conditions in total joint replacement. JBJS Rev. 2021 Dec 15;9(12). 3. Herrera A, Panisello JJ, Ibarz E, Cegoñino J, Puértolas JA, Gracia L. Long-term study of bone remodelling after femoral stem: a comparison between dexa and finite element simulation. J Biomech. 2007;40(16):3615-25. 4. Maloney WJ, Sychterz C, Bragdon C, McGovern T, Jasty M, Engh CA, Harris WH. The Otto Aufranc Award. Skeletal response to well fixed femoral components inserted with and without cement. Clin Orthop Relat Res. 1996 Dec;(333):15-26. 5. Venesmaa PK, Kröger HPJ, Miettinen HJA, Jurvelin JS, Suomalainen OT, Alhava EM. Monitoring of periprosthetic BMD after uncemented total hip arthroplasty with dual-energy X-ray absorptiometry—a 3-year follow-up study. J Bone Miner Res. 2001 Jun;16(6):1056-61. 6. Ohta H, Kobayashi S, Saito N, Nawata M, Horiuchi H, Takaoka K. Sequential changes in periprosthetic bone mineral density following total hip arthroplasty: a 3-year follow-up. J Bone Miner Metab. 2003;21(4):229-33. 7. Anderson PA, Morgan SL, Krueger D, Zapalowski C, Tanner B, Jeray KJ, Krohn KD, Lane JP, Yeap SS, Shuhart CR, Shepherd J. Use of bone health evaluation in orthopedic surgery: 2019 ISCD Official Position. J Clin Densitom. 2019 Oct-Dec;22(4):517-43. 8. Anderson PA, Jeray KJ, Lane JM, Binkley NC. Bone health optimization: Beyond Own the Bone: AOA Critical Issues. J Bone Joint Surg Am. 2019 Aug 7;101(15):1413-9. 9. Kadri A, Binkley N, Hare KJ, Anderson PA. Bone health optimization in orthopaedic surgery. J Bone Joint Surg Am. 2020 Apr 1;102(7):574-81. 10. Anderson PA, Freedman BA, Brox WT, Shaffer WO. Osteoporosis: recent recommendations and positions of the American Society for Bone and Mineral Research and the International Society for Clinical Densitometry. J Bone Joint Surg Am. 2021 Apr 21;103(8):741-7. 11. Leder BZ, O’Dea LS, Zanchetta JR, Kumar P, Banks K, McKay K, Lyttle CR, Hattersley G. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosi