This animal study compares different methods of performing an osteotomy, including using an Erbium-doped Yttrium Aluminum Garnet laser, histologically, radiologically and biomechanically. A total of 24 New Zealand rabbits were divided into four groups (Group I: multihole-drilling; Group II: Gigli saw; Group III: electrical saw blade and Group IV: laser). A proximal transverse diaphyseal osteotomy was performed on the right tibias of the rabbits after the application of a circular external fixator. The rabbits were killed six weeks after the procedure, the operated tibias were resected and radiographs taken. . The specimens were tested biomechanically using three-point bending forces, and four tibias from each group were examined histologically. Outcome parameters were the biomechanical stability of the tibias as assessed by the failure to load and radiographic and histological examination of the osteotomy site. . The osteotomies healed in all specimens both radiographically and histologically. The differences in the mean radiographic (p = 0.568) and histological (p = 0.71) scores, and in the mean failure loads (p = 0.180) were not statistically significant between the groups. . Different methods of performing an osteotomy give similar quality of union. The laser osteotomy, which is not widely used in orthopaedics is an alternative to the current methods. Cite this article: Bone Joint J 2015;97-B:1628–33

Autologous chondrocyte implantation is an option in the treatment of full-thickness chondral or osteochondral injuries which are symptomatic. The goal of surgery and rehabilitation is the replacement of damaged cartilage with hyaline or hyaline-like cartilage, producing improved levels of function and preventing early osteoarthritis. The intermediate results have been promising in terms of functional and clinical improvement. Our aim was to explore the hypothesis that the histological quality of the repair tissue formed after autologous chondrocyte implantation improved with increasing time after implantation. In all, 248 patients who had undergone autologous chondrocyte implantation had biopsies taken of the repair tissue which then underwent histological grading. Statistical analysis suggested that with doubling of the time after implantation the likelihood of a favourable histological outcome was increased by more than fourfold (p < 0.001)

Aims. A limited number of investigations with conflicting results have described perivascular lymphocytic infiltration (PVLI) in the setting of total knee arthroplasty (TKA). The purpose of this study was to determine if PVLI found in TKAs at the time of aseptic revision surgery was associated with worse clinical outcomes and survivorship. Methods. A retrospective review was conducted on 617 patients who underwent aseptic TKA revision who had histological analysis for PVLI at the time of surgery. Clinical and radiological data were obtained pre- and postoperatively, six weeks postoperatively, and then every year thereafter. Results. Within this cohort, 118 patients (19.1%) were found to have PVLI on histological analysis. Re-revision was performed on 83 patients (13.4%) with no significant differences in all-cause or aseptic revisions between groups. A higher incidence of PVLI was noted in female patients (p = 0.037). There was no significant difference in improvement in the range of motion (p = 0.536), or improvement of KSC (p = 0.66), KSP (p = 0.61), or KSF (p = 0.3) clinical outcome scores between PVLI and no PVLI sub-groups. There was a higher incidence of a preoperative diagnosis of pain in the PVLI group compared with patients without PVLI (p = 0.002) present. Conclusion. PVLI found on large-scale histological analysis in TKAs at aseptic revision surgery was not associated with worse clinical outcomes or rates of re-revision. Cite this article: Bone Joint J 2021;103-B(6 Supple A):145–149

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

Aims. To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm. 2. , 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results. In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion. ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352

Aims. Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect. Methods. A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus. Results. In vitro immunohistochemistry revealed that the meniscus cells migrated from the minced meniscus and proliferated in the gel. Furthermore, histological analysis suggested that the minced meniscus embedded in the atelocollagen gel produced tissue resembling the native meniscus in vivo. The minced meniscus group also had a higher Pauli’s score compared to the defect and atelocollagen groups. Conclusion. Our data show that cells in minced meniscus can proliferate, and that implantation of the minced meniscus within atelocollagen induces meniscus regeneration, thus suggesting a novel therapeutic alternative for meniscus tears. Cite this article: Bone Joint Res 2021;10(4):269–276

Abstract. Introduction. Several studies have reported significant cobalt(Co) and chromium(Cr) elevations in the blood of patients with total-knee-replacements (TKRs), and histological signs of metal sensitivity have been reported in up to 44% of patients undergoing revision of their TKRs. We carried out this investigation to determine the source and quantity of metal release in TKRs. Methodology. We identified all TKRs with polished CoCr trays (N=59) [Vanguard=29, Attune=4 and PFC=26]. These were analysed using peer-reviewed [coordinate-measuring-machine (CMM)] methodology to measure the volumetric wear of the polyethylene (PE) bearing surfaces and trays. The trays were analysed using 2D-profilometry (surface roughness-Ra) and 4D-microscopy. Histological and blood metal ion concentration analyses were performed. Results. The median(IQR) PE wear rate was 10(6to20) mm3/year. Microscopic analysis identified pitting on superior surface of 36(49%) trays. Ra [median (IQR)] of superior surface of pitted trays [0.076 (0.060–0.084) µm] showed a statistically significant increase (p<0.001) compared with unpitted trays [0.057(0.049–0.066) µm]. 4D-microscopy and CMM analysis estimated wear volumes of up to 2mm3 secondary to pitting. The median (range) Co and Cr concentrations were 2.5µg/l (0.2–69.4) and 1.7µg/l (0.5–12.5) respectively in 40 patients. Of the tissue samples examined in 30 patients,6 had at-least “mild”-ALVAL infiltrate. All corresponding “ALVAL” explants were found to be pitted and/or show evidence of loosening of the tray. Conclusion. This study provides further evidence that CoCr release in TKR appears to be an under-recognised cause of adverse clinical outcomes. Gross metal ion elevations occurred in association with micromotion/loosening of the tray

Abstract. Introduction. Articular cartilage degradation is a defining feature of osteoarthritis. Synovium is a reactive tissue with synovial villae, neoangiogenesis and intimal hyperplasia common to many joint pathologies. The consequences of cartilage debris in osteoarthritis impacting the synovial intima is not well understood. We analysed the immunohistology of synovium from 16 patients with osteoarthritis and 17 patients undergoing knee surgery for non-arthritic pathologies. This data was integrated with imaging and functional scores to correlate synovitis in osteoarthritis. Methodology. Formalin-fixed paraffin embedded synovial biopsy sections were cut in serial sequence and processed for routine staining (H&E or CD3, CD68, CD20, Vimentin, vWF and PCNA IHC) using standardised Dako monoclonal mouse anti-human antibodies. Digital images scanned at x20 were evaluated for fragments of cartilage and aggregates of inflammatory cells. Clinical data (gender, BMI, KL grade, WOMAC & SF-12 scores) was aligned with histopathological data. Results. Cartilage fragments were seen in the synovial intimal layer from end-stage osteoarthritis especially those with BMI<30kg/m2. Macrophages, T-cells and B-cells were identified surrounding cartilage inclusions. Inflammatory aggregates of T-cells, B-cells and macrophages were located peri-cartilage in the intima and peri-vascular in the sub-intimal layer of the synovium. Worse synovitis and function scores were significantly associated with both cartilage inclusions and inflammatory aggregates. X-ray features linked to longer duration of symptoms were associated with inflammatory aggregates. Conclusion. The histological features of the synovium clearly reflect deteriorating joint structures and compromised clinical function

Background. A limited number of investigations with conflicting results have described perivascular lymphocytic infiltration (PVLI) in the setting of total knee arthroplasty. The purpose of this study was to determine if PVLI found in total knee replacements at the time of aseptic revision surgery was associated with worse clinical outcomes and survivorship. Methods. A retrospective review was conducted on 617 patients that underwent aseptic total knee arthroplasty revision who had histologic analysis for PVLI at the time of surgery. Clinical and radiographic data was obtained pre and postoperatively, 6 weeks post operatively, and then every year thereafter. Results. Within this cohort, 118 patients (19.1%) were found to have PVLI on histologic analysis. A higher incidence of PVLI was noted in female patients (p = 0.037) and those patients with a preoperative diagnosis of unexplained pain (p=0.002). Re-revision was performed on 83 patients (13.4%) with no significant differences in all-cause or aseptic revisions between groups. There was no significant difference in range of motion improvement (p = 0.54), or improvement of KSC (p = 0.66), KSP (p = 0.61), or KSF (p = 0.3) clinical outcome scores between PVLI and no PVLI sub-groups. Conclusion. Perivascular lymphocytic infiltration found on large-scale histologic analysis in total knee replacements at aseptic revision surgery was not associated with worse clinical outcomes or difference in revision rates

Objectives. To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. Methods. Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. Results. Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 . sd. 1.7, T: mean 4.5 . sd. 0.5, p = 0.14; eight weeks, S: mean 5.8 . sd. 0.8, T: mean 4.8 . sd. 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 . sd. 1.2, T: mean 4.8 . sd. 0.4, p = 0.43; eight weeks, S: mean 5.3 . sd. 0.8,T: mean 5.5 . sd. 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 . sd. 9.0N and 13.1 . sd. 5.6N) or eight weeks (12.6 . sd. 3.6N and 17.1 . sd. 6.4N, respectively). Conclusion. Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods. Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327–335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2

Objectives. The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage. Methods. Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored. Results. The CBA group showed similar results to the autologous group in biomechanical properties, Moran’s criteria, histological tests and Wakitani histological scoring. Conclusions. These results suggest that tissue-engineered cartilage constructed using the CBA technique could be used effectively to repair cartilage defects in the weight-bearing area of joints. Cite this article: H. Lin, J. Zhou, L. Cao, H. R. Wang, J. Dong, Z. R. Chen. Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44 avidin binding technique for the repairing of cartilage defects in the weight-bearing area of knee joints in pigs. Bone Joint Res 2017;6:–295. DOI: 10.1302/2046-3758.65.BJR-2016-0277

Aims

Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

Aims

Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Background. Pseudotumor or high grade ALVAL (aseptic lymphocyte-dominated vasculitis-associated lesion) development around total hip replacements secondary to local metal debris generation – especially in the setting of metal-on-metal bearings – is a well-recognised histopathologic phenomenon. Recent work has suggested a strong genetic correlation with an individual's risk of such lesion development following metal exposure. Emerging data have highlighted a similar potential concern around total knee replacements (TKRs), particularly with increasing construct modularity. To date, the body-of-knowledge pertaining to TKR-associated ALVALs has largely been limited to individual case reports or small retrospective case series’, with no large-scale investigation looking at this potential complication. This study sought to establish the preliminary prevalence of pseudotumor or high grade ALVAL formation seen at the revision of primary TKRs and to establish the correlation between histologic ALVAL grade and patient-reported functional outcomes. Methods. Findings of 1263 consecutive patients undergoing revision knee surgery, at a high-volume referral center, were reviewed. 161 cases of active infection were excluded. Complete histopathology reports were subsequently available for 321 (29.1%) non-infective cases. Each case was independently histologically-classified using a previously validated scoring system reflecting ALVAL grade. Post-operative patient-reported outcomes measures (PROMs) were available for 134 patients (41.7%), allowing direct correlation between functional performance and the established histopathology results. Results. In total, 23 high grade lesions were identified, including 5 distinct pseudotumors, representing 7.2% (23/321) of the cohort. When compared by histologic grade, Jonkeere-Terpstra testing yielded P-values of 0.02 and 0.03 for the Oxford Knee Score and WOMAC datasets, respectively, suggesting a high correlation between ALVAL grade and functional knee scores. Conclusions. The results of this large histologic analysis suggest a prevalence of pseudotumor or high grade ALVAL development at revision TKR surgery of greater than 7%. This unexpectedly high result may contribute clinical insight into the previously under-appreciated significance of metal debris-related local tissue reactions around TKRs. The findings herein also demonstrate a strong near-linear inverse relationship between patient-reported clinical knee performance and the underlying histologic grade of local tissue reaction. Collectively, this information may provide some further understanding of a proportion of the widely quoted 15–20% of patients who remain dissatisfied with their TKR after surgery. This result has potential diagnostic and management implications for clinicians treating patients with underperforming in situ TKRs and should prompt consideration of an ALVAL secondary to local wear debris-generated metallosis in the differential diagnosis

Aims. Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function. Materials and Methods. A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6). Results. At eight weeks, FiberTape alone or FiberTape-augmented autograft demonstrated increased biomechanical stability compared with autograft regarding ultimate load to failure (p = 0.035), elongation (p = 0.006), and energy absorption (p = 0.022). FiberTape-grafted samples also demonstrated increased bone mineral density in the bone tunnel (p = 0.039). Histological evaluation showed integration of all grafts in the bone tunnels by new bone formation, and limited signs of inflammation overall. A lack of prolonged inflammation in all samples was confirmed by quantification of inflammation biomarkers. However, no regeneration of ligament-like tissue was observed along the suture tape materials. Except for one autograft failure, no adverse events were detected. Conclusion. Our results indicate that FiberTape increases the biomechanical performance of intra-articular ligament reconstructions in a verified rabbit model at eight weeks. Within this period, FiberTape did not adversely affect bone tunnel healing or invoke a prolonged elevation in inflammation. Cite this article: Bone Joint J 2019;101-B:1238–1247

Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831

Aims

The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process.

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Introduction. Initial post-operative implant instability leads to impaired osseointegration, one of the most common reasons for aseptic loosening and revision surgery. In this study, we developed a novel murine model of implant instability and demonstrated the anabolic effect of immediate and delayed intermittent Parathyroid Hormone (iPTH) treatment in the setting of instability-induced osseointegration failure. Methods. 3D-printed titanium implants were inserted in an oversized drill-hole in the tibia of C57Bl/6 mice (n=54). After implantation, the mice were randomly divided in 3 treatment groups (control: PBS-vehicle; iPTH; delayed iPTH). Radiographic analysis was performed to confirm signs of implant loosening. Peri-implant tissue formation was assessed through histology. Osseointegration was assessed through µCT and biomechanical pullout testing. Results. Immediate iPTH treatment reduced radiolucencies and induced a distinct pedestal sign distal to the implant stem (white arrow Fig 1A). The PBS treated mice had fibrous tissue implant encapsulation, whereas new mineralized tissue and no fibrous tissue was observed with immediate iPTH treatment (Fig 1E). Delayed iPTH treatment was also able to exhibit significant peri-implant bone mineralization, osteoblasts, angiogenesis, and a reduction of fibrous tissue (Fig 2A-B). iPTH treatment increased the force required to pull out the implant significantly from 8.41 ± 8.15N in the PBS group to 21.49 ± 10.45N and 23.68 ± 8.99N, in the immediate and delayed iPTH treatment groups, respectively (Fig 2D). PBS vehicle resulted in a bone volume/trabecular volume (BV/TV) of 0.23 ± 0.03, while immediate and delayed iPTH treatment increased BV/TV significantly to 0.46 ± 0.07 and 0.34 ± 0.10, respectively (Fig 2E). Conclusion. Immediate iPTH treatment prevents peri-implant fibrous tissue formation and enhances peri-implant bone formation in our murine model of mechanical instability. Delayed iPTH treatment was able to resolve the peri-implant fibrous tissue and stimulate bone formation. This study potentially addresses a leading cause of aseptic loosening by demonstrating that initial implant instability can be rescued by iPTH even with delayed start of treatment. For any figures or tables, please contact authors directly