In vitro injection of osteoporotic cadaveric femurs with a triphasic calcium‐based implant confers immediate biomechanical integrity

Abstract

Current pharmaceutical therapies can reduce hip fractures by up to 50%, but compliance to treatment is low and therapies take up to 18 months to reduce risk. Thus, alternative or complementary approaches to reduce the risk of hip fracture are needed. The AGN1 local osteo‐enhancement procedure (LOEP) is one such alternative approach, as it is designed to locally replace bone lost due to osteoporosis and provide immediate biomechanical benefit. This in vitro study evaluated the initial biomechanical impact of this treatment on human cadaveric femurs. We obtained 45 pairs of cadaveric femurs from women aged 77.8 ± 8.8 years. One femur of each pair was treated, while the contralateral femur served as an untreated control. Treatment included debridement, irrigation/suction, and injection of a triphasic calcium‐based implant (AGN1). Mechanical testing of the femora was performed in a sideways fall configuration 24 h after treatment. Of the 45 pairs, 4 had normal, 16 osteopenic, and 25 osteoporotic BMD T‐scores. Altogether, treatment increased failure load on average by 20.5% ( p < 0.0001). In the subset of osteoporotic femurs, treatment increased failure load by 26% and work to failure by 45% ( p < 0.01 for both). Treatment did not significantly affect stiffness in any group. These findings provide evidence that local delivery of the triphasic calcium‐based implant in the proximal femur is technically feasible and provides immediate biomechanical benefit. Our results provide strong rationale for additional studies investigating the utility of this approach for reducing the risk of hip fracture. © 2019 The Authors. Journal of Orthopaedic Research ® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

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

“…The consistency and magnitude of the increases in femoral strength combined with the sustained nature of the femoral strength gains through 5-7 years indicate that AGN1 LOEP likely provides a long-term benefit to osteoporotic subjects. In addition to the likely long-term benefit, a prior study in human cadaveric femurs demonstrated that AGN1 implantation also leads to an immediate increase in femoral strength [18]. Although the sample size does not allow for a statistical assessment of fracture reduction, increased aBMD and femoral strength via FEA correlates with bone strength and fracture risk reduction [19,20,22,23], suggesting that AGN1 LOEP has the potential to reduce hip fracture risk.…”

“…Real-world hip fracture prevention with drug therapy is further limited due to under-diagnosis of osteoporosis, limited prescription of pharmaceutical therapies to osteoporotic patients, delayed onset of effectiveness of these therapies, and an incomplete 30 to 51% hip fracture risk reduction [11,24,26,28]. In contrast, AGN1 LOEP provides immediate [18] and as noted above, long-term protection, and compliance is guaranteed as the treatment is a one-time procedure. Moreover, the AGN1 LOEP treatment response was observed in all subjects whether or not they were taking anti-resorptive drugs, demonstrating the feasibility of using AGN1 LOEP in patients on systemic osteoporosis therapy.…”

“…In this study, we investigated the AGN1 local osteoenhancement procedure (LOEP), a minimally-invasive surgical approach to prepare an enhancement site, the area where new bone is desired within a local bony region weakened by osteoporotic bone loss, and to fill that site with a triphasic, resorbable, calcium-based implant material. This approach involves a single treatment that provides immediate strengthening [18], followed by resorption of the implant material and replacement with new bone.…”

Cadaveric Stem Cells: Their Research Potential and Limitations

“…The simple protocol for collecting and storing the skin from dead donors makes possible the successive skin transplants in patients with extensive burns, decreasing their mortality or in the therapy of hard-to-heal wounds ( Sachkov et al, 2018 ), including lower limbs ulcers not susceptible to other treatment ( Mosti et al, 2020 ). Additionally, postmortem collected bones, due to keeping their mechanical properties after the death, served as research material in studies evaluating the effect of local bone reinforcement by injecting a three-phase calcium-based implant, the novel osteoporosis treatment ( Stroncek et al, 2019 ). Postmortem collected bone fragments can be frozen up to eight times without losing their morphological and biomechanical properties.…”

Local osteo-enhancement of osteoporotic vertebra with a triphasic bone implant material increases strength—a biomechanical study

“…A local osteo-enhancement procedure utilizing resorbable, triphasic calcium sulfate/calcium phosphate injectable implant material is under clinical investigation as a means of preventing osteoporotic hip fractures. The implant material increased the fracture strength of cadaveric osteoporotic femurs [9]. This approach to strengthening at risk osteoporotic vertebra has not been previously studied.…”