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      In vitro osteogenic capacity of bone marrow MSCs from postmenopausal women reflect the osseointegration of their cementless hip stems

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          Abstract

          Age-related dysfunction of mesenchymal stromal cells (MSCs) is suggested as a main cause of altered bone repair with aging. We recently showed that in postmenopausal women undergoing cementless total hip arthroplasty (THA) aging, low bone mineral density (BMD) and age-related geometric changes of the proximal femur are risk factors for increased early migration and delayed osseointegration of the femoral stems. Extending these analyses, we have here explored how the in vitro osteogenic capacity of bone marrow MSCs from these patients reflects implant osseointegration, representing the patient's in vivo bone healing capacity. A total of 19 postmenopausal women with primary hip osteoarthritis (mean age 65 years, range 50–78) and well-defined bone quality underwent successful preoperative in vitro analysis of osteogenic capacity of iliac crest bone marrow MSCs as well as two-year radiostereometric (RSA) follow-up of femoral stem migration after cementless THA. In patients with MSCs of low osteogenic capacity, the magnitude of cumulative stem subsidence after the settling period of three months was greater ( p = 0.028) and the time point for translational osseointegration was significantly delayed ( p = 0.030) compared to patients with MSCs of high osteogenic capacity. This study suggests that patients with MSCs of low in vitro osteogenic capacity may display increased stem subsidence after the settling period of 3 months and thereby delayed osseointegration. Our study presents a novel approach for studying the biological progress of hip implant osseointegration and to verify the impact of decreased MSCs function, especially in patients with age-related dysfunction of MSCs and bone healing capacity.

          Highlights

          • Age-related dysfunction of MSCs is a main cause of altered bone repair with aging.

          • MSCs play a critical role in osseointegration of cementless hip replacement.

          • We explored if hip implant osseointegration in postmenopausal women is mirrored by in vitro osteogenic ability of their MSCs.

          • Low osteogenic differentiation of MSCs correlated with increased implant migration.

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          Most cited references37

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          Osseointegrated implants in the treatment of the edentulous jaw. Experience from a 10-year period.

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            Osseointegrated titanium implants. Requirements for ensuring a long-lasting, direct bone-to-implant anchorage in man.

            A total of 2895 threaded, cylindrical titanium implants have been inserted into the mandible or the maxilla and 124 similar implants have been installed in the tibial, temporal or iliac bones in man for various bone restorative procedures. The titanium screws were implanted without the use of cement, using a meticulous technique aiming at osseointegration--a direct contact between living bone and implant. Thirty-eight stable and integrated screws were removed for various reasons from 18 patients. The interface zone between bone and implant was investigated using X-rays, SEM, TEM and histology. The SEM study showed a very close spatial relationship between titanium and bone. The pattern of the anchorage of collagen filaments to titanium appeared to be similar to that of Sharpey's fibres to bone. No wear products were seen in the bone or soft tissues in spite of implant loading times up to 90 months. The soft tissues were also closely adhered to the titanium implant, thereby forming a biological seal, preventing microorganism infiltration along the implant. The implants in many cases had been allowed to permanently penetrate the gingiva and skin. This caused no adverse tissue effects. An intact bone-implant interface was analyzed by TEM, revealing a direct bone-to-implant interface contact also at the electron microscopic level, thereby suggesting the possibility of a direct chemical bonding between bone and titanium. It is concluded that the technique of osseointegration is a reliable type of cement-free bone anchorage for permanent prosthetic tissue substitutes. At present, this technique is being tried in clinical joint reconstruction. In order to achieve and to maintain such a direct contact between living bone and implant, threaded, unalloyed titanium screws of defined finish and geometry were inserted using a delicate surgical technique and were allowed to heal in situ, without loading, for a period of at least 3--4 months.
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              Roentgenographic assessment of the biologic fixation of porous-surfaced femoral components.

              Certain roentgenographic signs have value in predicting the fixation of a cementless femoral component to bone by osseointegration. Other signs have value in predicting the gross stability of a cementless femoral component. The authors have determined the specificity and sensitivity of the signs for osseointegration in cases in which the histologic fixation has been confirmed after implant removal. The authors have also determined the specificity and sensitivity of the signs for gross implant stability in cases in which the stability has been confirmed at reoperation. Statistical methods were used to determine a numeric value for each of these roentgenographic signs, and these values were combined into a score. The score was divided into fixation by osseointegration and mechanical implant stability. The two scores were then combined into an overall score. When signs of osseointegration were present, the implant was always stable, and the overall scores were the highest. When signs of osseointegration were absent, the mechanical stability varied, and the scores were lower. A neutral or slightly negative score correlated with failed osseointegration but secondary successful implant stabilization. A very low negative score correlated with gross implant instability. To confirm the validity of the scoring system, the two-year postoperative score was determined for 1005 cases in which the clinical outcome was known. A strong correlation between the presence of symptoms and a low score confirmed the value of the scoring system for diagnosing implant loosening as the cause of symptoms. As a second test, the two-year and five-year postoperative results were compared in the same patients. A high two-year score correlated with durable implant stability through five years. A low two-year score correlated with a higher incidence of late symptomatic loosening.
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                Author and article information

                Contributors
                Journal
                Bone Rep
                Bone Rep
                Bone Reports
                Elsevier
                2352-1872
                25 May 2016
                December 2016
                25 May 2016
                : 5
                : 124-135
                Affiliations
                Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku/Turku University Hospital, Turku, Finland
                Author notes
                [* ]Corresponding author at: Orthopaedic Research Unit, University of Turku/Turku University Hospital, Turku, Finland.Orthopaedic Research UnitUniversity of Turku/Turku University HospitalTurkuFinland hannu.aro@ 123456utu.fi
                Article
                S2352-1872(16)30020-1
                10.1016/j.bonr.2016.05.005
                4926811
                8e0f156a-5d53-4808-a3b6-44f8eb663c4a
                © 2016 The Authors. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 December 2015
                : 25 April 2016
                : 20 May 2016
                Categories
                Article

                human mesenchymal stromal cells,osteogenic differentiation,radiostereometric analysis,total hip arthroplasty,osseointegration

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