Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study

J G Howe, R S Hill, J D Stroncek, J L Shaul, D Favell, R R Cheng, K Engelke, H K Genant, D C Lee, T M Keaveny, M L Bouxsein, B Huber, J G Howe, R S Hill, J D Stroncek, J L Shaul, D Favell, R R Cheng, K Engelke, H K Genant, D C Lee, T M Keaveny, M L Bouxsein, B Huber

Abstract

This first-in-human study of AGN1 LOEP demonstrated that this minimally-invasive treatment durably increased aBMD in femurs of osteoporotic postmenopausal women. AGN1 resorption was coupled with new bone formation by 12 weeks and that new bone was maintained for at least 5-7 years resulting in substantially increased FEA-estimated femoral strength.

Introduction: This first-in-human study evaluated feasibility, safety, and in vivo response to treating proximal femurs of postmenopausal osteoporotic women with a minimally-invasive local osteo-enhancement procedure (LOEP) to inject a resorbable triphasic osteoconductive implant material (AGN1).

Methods: This prospective cohort study enrolled 12 postmenopausal osteoporotic (femoral neck T-score ≤ - 2.5) women aged 56 to 89 years. AGN1 LOEP was performed on left femurs; right femurs were untreated controls. Subjects were followed-up for 5-7 years. Outcomes included adverse events, proximal femur areal bone mineral density (aBMD), AGN1 resorption, and replacement with bone by X-ray and CT, and finite element analysis (FEA) estimated hip strength.

Results: Baseline treated and control femoral neck aBMD was equivalent. Treated femoral neck aBMD increased by 68 ± 22%, 59 ± 24%, and 58 ± 27% over control at 12 and 24 weeks and 5-7 years, respectively (p < 0.001, all time points). Using conservative assumptions, FEA-estimated femoral strength increased by 41%, 37%, and 22% at 12 and 24 weeks and 5-7 years, respectively (p < 0.01, all time points). Qualitative analysis of X-ray and CT scans demonstrated that AGN1 resorption and replacement with bone was nearly complete by 24 weeks. By 5-7 years, AGN1 appeared to be fully resorbed and replaced with bone integrated with surrounding trabecular and cortical bone. No procedure- or device-related serious adverse events (SAEs) occurred.

Conclusions: Treating femurs of postmenopausal osteoporotic women with AGN1 LOEP results in a rapid, durable increase in aBMD and femoral strength. These results support the use and further clinical study of this approach in osteoporotic patients at high risk of hip fracture.

Keywords: Bone mineral density; Femoral strength; Finite element analysis; Hip fracture; LOEP; Local osteo-enhancement procedure; Osteoporosis; proximal femur.

Conflict of interest statement

JGH is the founder and a shareholder of AgNovos. RSH, JDS, JLS, DF, and RRC are/were employees and shareholders of AgNovos. HKG has received honoraria, consulting fees, and speaker fees from AgNovos, Medtronic, Regeneron, BioMarin, Clementia, Amgen, Lilly, Daiichi, AstraZeneca, and MedImmune. MB has received consulting fees from AgNovos and research funding from Radius and Amgen. DCL is an employee of and has equity interest in O.N. Diagnostics. TMK is the founder, shareholder, and consulting Chief Science Officer of O.N. Diagnostics and has received consulting fees from AgNovos, O.N. Diagnostics, and Amgen. BH has received consulting fees from and is a shareholder of AgNovos.

Figures

Fig. 1
Fig. 1
Fluoroscopic series showing key steps in AGN1 LOEP. a Insertion of the guide pin to the apex of the femoral neck. b Cannulated drill advancement over the guide pin to the subcapital epiphyseal scar. c Gentle debridement to define the enhancement site followed by irrigation to remove loose elements. d Injection of the implant material to fill the enhancement site
Fig. 2
Fig. 2
Representative X-ray series from subject 07 showing AGN1 resorption and replacement with new bone in the proximal femur; left to right: pre-treatment, post-treatment 12 weeks, 24 weeks, and 311 weeks
Fig. 3
Fig. 3
CT series from subject 06 (top row) and Subject 11 (bottom row) showing paucity of trabeculae in the femoral neck at baseline, and subsequent formation and remodeling of new bone; left to right: Pre-treatment, Post-treatment 12 weeks, 24 weeks, and at the extension follow-up average of 6 years
Fig. 4
Fig. 4
Femoral neck aBMD in treated and control hips as assessed by DXA. N = 12 except at 315 weeks N = 10; p < 0.001 treated vs control for all time points

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