Osteoclast differentiation in rheumatoid arthritis.

Osteoclasts, derived from the monocyte/macrophage line of bone marrow hematopoietic stem cell progenitors, are the sole bone-resorbing cells of the body. Conventional osteoclast differentiation requires macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. Rheumatoid arthritis (RA) is the most prevalent systemic autoimmune disease and inflammatory arthritis characterized by bone destruction. Increased levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in the serum and joints, cause excessive bone destruction. We have recently reported that stimulation of human peripheral blood monocytes with TNF-α and IL-6 induces the differentiation of osteoclasts with bone resorption activity. This review presents the functional differences between representative osteoclasts, conventional RANKL-induced osteoclasts, and recently identified proinflammatory cytokine (TNF-α and IL-6)-induced osteoclasts in RA patients. We believe novel pathological osteoclasts associated with RA will be identified, and new therapeutic strategies will be developed to target these osteoclasts and prevent the progression of bone destruction.

Bone Flap Resorption After Cranioplasty: Risk Factors and Proposal of the Flap Integrity Score.

BACKGROUND: Bone flap resorption is a known complication of postdecompressive autologous cranioplasty. Although several potential etiopathogenetic factors have been investigated, their role is still under discussion. To further complicate things, resorption is not an all-or-nothing event, patients frequently presenting with different degrees of flap remodeling. Focus of this paper was to describe the elaboration of a score quantifying bone resorption according to a set of clinical and radiological criteria, hopefully allowing prompt identification of patients needing resurgery before the development of adverse events. METHODS: In a 10-year period, 281 autologous cranioplasties were performed at our institution following decompressive craniectomy. Pertinent clinical and radiological information was registered. A set of 3 clinical and 3 radiological parameters was established to score the degree of resorption, identified under the acronym FIS (Flap Integrity Score). Three groups of patients emerged, respectively showing no (208), partial (32), and advanced (41) resorption. RESULTS: An overall 14.6% incidence of advanced bone resorption was found in our series. Younger age, bone multifragmentation, higher postcranioplasty Glasgow Outcome Scale scores, <2 cm distance of medial craniectomy border from the midline, and cause leading to decompressive craniectomy were associated to a statistically significant higher risk of developing a relevant bone flap resorption. The first three variables were confirmed as risk factors in multivariate analysis. Flap Integrity Score well discriminated the 3 different groups. CONCLUSIONS: Autologous bone repositioning is still a valuable, low-cost, cosmetically and functionally satisfactory procedure. Nonetheless, although resorption affects a minor percentage of patients, its early identification and treatment can improve long-term results.

Autologous Cranioplasty with Bone Flap Preserved in Conventional Freezers: An Adequate Option in Low Resource Settings.

BACKGROUND: Autologous cranioplasty has been used for decades and is the gold standard treatment in patients who underwent decompressive craniectomy (DC). One of the most common methods to store the cranial bone flap is cryopreservation at very low temperatures (-70 to -80°). The only way to achieve these low temperatures is by using special freezers which are not always available in all medical facilities, especially in low-resource centers. This paper describes our experience with the storage of cranial bone flaps in freezers of conventional refrigerators. METHODS: This retrospective study included patients treated with autologous cranioplasty, operated between 2015 and 2020. The cranial bone flap was stored at -18°C in the freezer of conventional refrigerators. Complications and outcomes were analyzed and compared with reports of patients in whom ultra-low temperature freezers were used for bone flap preservation. RESULTS: Twenty-five patients were included. The average follow-up period was 33 months. Trauma was the most common cause of DC, followed by stroke. The mean age was 36.7. Aseptic bone flap resorption was observed in 4 cases (16%). No cases of infection were observed. CONCLUSIONS: The use of freezers from conventional refrigerators may be an acceptable alternative for the preservation of the cranial bone flap in facilities where special freezers are not available. The rate of aseptic bone necrosis and infections observed in this paper was similar to the incidence of these complications reported in studies where ultra-low temperatures were used.

The potential role of mechanotransduction in the management of pediatric calvarial bone flap repair.

Pediatric patients suffering traumatic brain injuries may require a decompressive craniectomy to accommodate brain swelling by removing a portion of the skull. Once the brain swelling subsides, the preserved calvarial bone flap is ideally replaced as an autograft during a cranioplasty to restore protection of the brain, as it can reintegrate and grow with the patient during immature skeletal development. However, pediatric patients exhibit a high prevalence of calvarial bone flap resorption post-cranioplasty, causing functional and cosmetic morbidity. This review examines possible solutions for mitigating pediatric calvarial bone flap resorption by delineating methods of stimulating mechanosensitive cell populations with mechanical forces. Mechanotransduction plays a critical role in three main cell types involved with calvarial bone repair, including mesenchymal stem cells, osteoblasts, and dural cells, through mechanisms that could be exploited to promote osteogenesis. In particular, physiologically relevant mechanical forces, including substrate deformation, external forces, and ultrasound, can be used as tools to stimulate bone repair in both in vitro and in vivo systems. Ultimately, combating pediatric calvarial flap resorption may require a combinatorial approach using both cell therapy and bioengineering strategies.

The effect of periprosthetic bone loss on the failure risk of tibial total knee arthroplasty.

The effect of long-term periprosthetic bone loss on the process of aseptic loosening of tibial total knee arthroplasty (TKA) is subject to debate. Contradicting studies can be found in literature, reporting either bone resorption or bone formation before failure of the tibial tray. The aim of the current study was to investigate the effects of bone resorption on failure of tibial TKA, by simulating clinical postoperative bone density changes in finite element analysis (FEA) models and FEA models were created of two tibiae representing cases with good and poor initial bone quality which were subjected to a walking configuration and subsequently to a traumatic stumbling load. Bone failure was simulated using a crushable foam model incorporating progressive yielding. Repetitive loading under a level walking load did not result in failure of the periprosthetic bone in neither the good nor poor bone quality tibia at the baseline bone densities. When applying a stumble load, a collapse of the tibial reconstruction was noticed in the poor bone quality model. Incorporating postoperative bone loss led to a significant increase of the failure risk, particularly for the poor bone quality model in which subsidence of the tibial component was substantial. Our results suggest bone loss can lead to an increased risk of a collapse of the tibial component, particularly in case of poor bone quality at the time of surgery. The study also examined the probability of medial or lateral subsidence of the implant and aimed to improve clinical implications. The FEA model simulated plastic deformation of the bone and implant subsidence, with further validation required via mechanical experiments.

Treatment of Glenoid Wear with the Use of Augmented Glenoid Components in Total Shoulder Arthroplasty: A Scoping Review.

¼ Treatment of glenoid bone loss continues to be a challenge in total shoulder arthroplasty (TSA). Although correcting glenoid wear to patient's native anatomy is desirable in TSA, there is lack of consensus regarding how much glenoid wear correction is acceptable and necessary in both anatomic and reverse TSA.¼ Use of augmented glenoid components is a relatively new treatment strategy for addressing moderate-to-severe glenoid wear in TSA. Augmented glenoid components allow for predictable and easy correction of glenoid wear in the coronal and/or axial planes while at the same time maximizing implant seating, improving rotator cuff biomechanics, and preserving glenoid bone stock because of off-axis glenoid reaming.¼ Augmented glenoid components have distinct advantages over glenoid bone grafting. Glenoid bone grafting is technically demanding, adds to the surgical time, and carries a risk of nonunion and graft resorption with subsequent failure of the glenoid component.¼ The use of augmented glenoid components in TSA is steadily increasing with easy availability of computed tomography-based preoperative planning software and guidance technology (patient-specific instrumentation and computer navigation).¼ Although different augment designs (full wedge, half wedge, and step cut) are available and a particular design may provide advantages in specific glenoid wear patterns to minimize bone removal (i.e. a half wedge in B2 glenoids), there is no evidence to demonstrate the superiority of 1 design over others.

[Long-term effectiveness of uncemented allograft-prosthesis composite for reconstruction of bone defects after proximal femur tumor resection].

Objective: To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection. Methods: Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded. Results: All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients. Conclusion: Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.

Micheliolide prevents estrogen deficiency-induced bone loss via inhibiting osteoclast bone resorption.

Osteoporosis is one of the major health problems characterized by decreased bone density and increased risk of fractures. Nowadays, the treating strategies against osteoporosis are efficient, but still have some drawbacks. Micheliolide, a guaianolide sesquiterpene lactone isolated from Michelia compressa and Michelia champac, has been reported to have anti-inflammatory effects. Here, our data suggest that Micheliolide could protect mice from ovariectomy induced bone loss. According to the Micro-CT scan and histomorphometry quantification data, Micheliolide treatment inhibits excessive osteoclast bone resorption without affecting bone formation in estrogen deficiency mice. Consistently, our data suggest that Micheliolide could inhibit osteoclastogenesis in vitro. Additionally, we confirmed that Micheliolide inhibits osteoclasts formation via inhibiting P38 MAPK signaling pathway, and P79350 (a P38 agonist) could rescue this effect. In summary, our data suggest that Micheliolide could ameliorate estrogen deficiency-induced bone loss via attenuating osteoclastogenesis. Hence, Micheliolide could be used as a novel anti-resorptive agent against osteoporosis.

Bone resorption of vertebral bodies at the operative segment after prevail cervical interbody fusion: A case report.

BACKGROUND: We report an interesting case of bone resorption of vertebral bodies at the operative segment after Peek Prevail cervical interbody fusion. Instability of cervical vertebrae is likely to occur due to increased stress in Peek Prevail implant body for bone resorption. The finite element analysis was used to clarify the biomechanical effects of bone resorption and stress distribution in Peek Prevail implant body. METHODS: We reported the case of a 48-year-old male patient who underwent Peek Prevail cervical interbody fusion and exhibited bone resorption 1 month after the surgery in X-ray of cervical vertebra. The degree of bone resorption was aggravated 2 months after surgery. Bone resorption in 3 months was similar to that in 2 months. We established a 3D reconstruction of the surgical segment in this case using Mimics software (vision 20.0) to generate basic boss resorption model. We simulated models of bone resorption using Ansys 17.0. The stress distribution of the contact surface between the screw and bone was analyzed under 6 conditions: flexion, extension, left and right flexion, and left and right rotation. RESULTS: The loading conditions affected the stress distribution in the implant body. When bone resorption occurred, the stress distribution of the contact surface between screw and bone focus in the tip of the screw increased sharply. CONCLUSION: Bone resorption of vertebral bodies in the operative segment may be a potential complication after Peek Prevail cervical interbody fusion. Great attention must be paid when bone resorption was occurred in order to avoid screw loosening before vertebral fusion.

Medial tibial bone resorption following total knee arthroplasty comparing a traditional with a kinematic design.

BACKGROUND: New total knee prostheses are being designed to improve clinical outcome, survivorship and patient satisfaction following total knee arthroplasty (TKA). A new knee system was developed with improvements in patellofemoral joint, trochlear geometry, polyethylene formulation and tibial baseplate. Aim of this study was to compare the newer kinematic knee system with its existing predecessor knee system in terms of clinical outcome, revision rates, radiographic outcomes specifically medial tibial bone resorption. METHODS: The prospective matched-pair study included 88 TKA surgeries using newer kinematic design knee prostheses, performed between January 2015 and December 2016, out of which 82 patients were available for final follow-up. The control cohort of 82 traditional TKA prosthesis was matched in terms of age, gender and body mass index. All surgeries were performed by the single surgeon using medial parapatellar arthrotomy and posterior stabilized implants were used. Clinical outcomes were assessed using knee society score, range of motion (ROM), anterior knee pain and crepitation. Radiological examinations included recording of radiolucent lines and medial tibial bone resorption. RESULTS: At the 5-year follow-up, no significant differences were noted in terms of mean knee society score (93.3 ± 6.6 vs 94.2 ± 8.1), knee function score (88.5 ± 10.5 vs 89.1 ± 11.2) and ROM. The incidences of anterior knee pain and crepitation were lower in the newer group (8.5% vs 21.9% and 14.6% vs 32.9%, respectively) compared to the traditional prosthesis group. No cases of aseptic loosening were observed in either cohort. No significant difference was seen in terms of radiolucent lines (29.3% vs 26.8%) and medial tibial resorption (2.43% in each group) incidences. CONCLUSIONS: At the 5 years follow-up no significant differences were noted between the two groups in terms of clinical and radiological outcomes, except the former proved to be better for anterior knee pain and crepitation. LEVEL OF EVIDENCE: II.

Condylar Resorption After Orthognathic Surgery: A Review of Risk Factors With a Proposed Algorithm of Treatment.

This study aimed to critically reanalyze systematic reviews of patients suffering from condylar resorption (CR) and summarize the current scientific pieces of evidence with a focus on a possible relationship between CR and orthognathic surgery (OS). The work followed the "Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol" guidelines and was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42020168660). The search strategy produced 143 articles. After reading the abstracts, 113 articles were excluded, and the full-text articles in English of the remaining 30 studies were separately examined for eligibility by 2 authors, with 20 of them being excluded because they did not meet the inclusion criteria. Finally, 10 systematic reviews were processed for critical evaluation. Young female patients with a high mandibular plane angle, diminished posterior facial height, posteriorly inclined condylar neck, and a counter-clockwise jaw rotation, are more likely to develop CR after OS. The most common procedure associated with CR in the included systematic reviews was the bimaxillary OS followed by bilateral sagittal split osteotomy. Hence, extreme caution and surgical modification should be used in these high-risk conditions. There is still a need for more evidence on the risks of OS or iatrogenic factors during the fixation of various osteosynthesis devices because it is still inconclusive and requires further justification.

Urinary collagen peptides: Source of markers for bone metabolic processes in kidney transplant recipients.

INTRODUCTION: Kidney transplant recipients (KTRs) are at an increased risk of fractures. Total urinary hydroxyproline excretion served as marker for bone resorption (BR) but was replaced by ß-CrossLaps (CTX), a C-terminal collagen α-1(I) chain (COL1A1) telopeptide. We investigated the low-molecular-weight urinary proteome for peptides associated with changes in bone metabolism after kidney transplantation. METHODS: Clinical and laboratory data including serum levels of CTX in 96 KTR from two nephrology centers were correlated with signal intensities of urinary peptides identified by capillary electrophoresis mass spectrometry. RESULTS: Eighty-two urinary peptides were significantly correlated with serum CTX levels. COL1A1 was the predominant peptide source. Oral bisphosphonates were administered for decreased bone density in an independent group of 11 KTR and their effect was evaluated on the aforementioned peptides. Study of the peptides cleavage sites revealed a signature of Cathepsin K and MMP9. Seventeen of these peptides were significantly associated with bisphosphonate treatment, all showing a marked reduction in their excretion levels compared to baseline. DISCUSSION: This study provides strong evidence for the presence of collagen peptides in the urine of KTR that are associated with BR and that are sensitive to bisphosphonate treatment. Their assessment might become a valuable tool to monitor bone status in KTR.

Role of Mast-Cell-Derived RANKL in Ovariectomy-Induced Bone Loss in Mice.

Mast cells may contribute to osteoporosis development, because patients with age-related or post-menopausal osteoporosis exhibit more mast cells in the bone marrow, and mastocytosis patients frequently suffer from osteopenia. We previously showed that mast cells crucially regulated osteoclastogenesis and bone loss in ovariectomized, estrogen-depleted mice in a preclinical model for post-menopausal osteoporosis and found that granular mast cell mediators were responsible for these estrogen-dependent effects. However, the role of the key regulator of osteoclastogenesis, namely, receptor activator of NFκB ligand (RANKL), which is secreted by mast cells, in osteoporosis development has, to date, not been defined. Here, we investigated whether mast-cell-derived RANKL participates in ovariectomy (OVX)-induced bone loss by using female mice with a conditional Rankl deletion. We found that this deletion in mast cells did not influence physiological bone turnover and failed to protect against OVX-induced bone resorption in vivo, although we demonstrated that RANKL secretion was significantly reduced in estrogen-treated mast cell cultures. Furthermore, Rankl deletion in mast cells did not influence the immune phenotype in non-ovariectomized or ovariectomized mice. Therefore, other osteoclastogenic factors released by mast cells might be responsible for the onset of OVX-induced bone loss.

Casticin suppresses RANKL­induced osteoclastogenesis and prevents ovariectomy­induced bone loss by regulating the AKT/ERK and NF­κB signaling pathways.

Postmenopausal osteoporosis is a systemic metabolic disease that chronically endangers public health and is typically characterized by low bone mineral density and marked bone fragility. The excessive bone resorption activity of osteoclasts is a major factor in the pathogenesis of osteoporosis; therefore, strategies aimed at inhibiting osteoclast activity may prevent bone decline and attenuate the process of osteoporosis. Casticin (Cas), a natural compound, has anti­inflammatory and antitumor properties. However, the role of Cas in bone metabolism remains largely unclear. The present study found that the receptor activator of nuclear factor­κΒ (NF­κB) ligand­induced osteoclast activation and differentiation were inhibited by Cas. Tartrate­resistant acid phosphatase staining revealed that Cas inhibited osteoclast differentiation, and bone resorption pit assays demonstrated that Cas affected the function of osteoclasts. Cas significantly reduced the expression of osteoclast­specific genes and related proteins, such as nuclear factor of activated T cells, cytoplasmic 1 and c­Fos at the mRNA and protein level in a concentration­dependent manner. Cas inhibited osteoclast formation by blocking the AKT/ERK and NF­κB signaling pathways, according to the intracellular signaling analysis. The microcomputed tomography and tissue staining of tibiae from ovariectomized mice revealed that Cas prevented the bone loss induced by estrogen deficiency and reduced osteoclast activity in vivo. Collectively, these findings indicated that Cas may be used to prevent osteoporosis.

Aspirin prevents estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis and promoting osteogenesis.

BACKGROUND: Aspirin is a commonly used antipyretic, analgesic, and anti-inflammatory drug. Numerous researches have demonstrated that aspirin exerts multiple biological effects on bone metabolism. However, its spatiotemporal roles remain controversial according to the specific therapeutic doses used for different clinical conditions, and the detailed mechanisms have not been fully elucidated. Hence, in the present study, we aimed to identify the dual effects of different aspirin dosages on osteoclastic activity and osteoblastic bone formation in vitro and in vivo. METHODS: The effects of varying doses of aspirin on osteoclast and osteoblast differentiation were evaluated in vitro. The underlying molecular mechanisms were detected using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence techniques. An ovariectomized rat osteoporosis model was used to assess the bone-protective effects of aspirin in vivo. RESULTS: Aspirin dose-dependently suppressed RANKL-induced osteoclasts differentiation and bone resorption in vitro and reduced the expression of osteoclastic marker genes, including TRAP, cathepsin K, and CTR. Further molecular analysis revealed that aspirin impaired the RANKL-induced NF-κB and MAPK signaling pathways and prevented the nuclear translocation of the NF-κB p65 subunit. Low-dose aspirin promoted osteogenic differentiation, whereas these effects were attenuated when high-dose aspirin was administered. Both low and high doses of aspirin prevented bone loss in an ovariectomized rat osteoporosis model in vivo. CONCLUSION: Aspirin inhibits RANKL-induced osteoclastogenesis and promotes osteogenesis in a dual regulatory manner, thus preventing bone loss in vivo. These data indicate that aspirin has potential applications in the prevention and treatment of osteopenia.

Probucol suppresses osteoclastogenesis via activating Nrf2 signaling and ameliorates ovariectomy-induced bone loss.

Osteoporosis is a systemic and endocrine bone disorder distinguished by declined bone mineral density, compromised bone strength, and destruction of trabecular structure. The abnormally excessive osteoclastogenesis and bone erosion play imperative roles in the progression of osteoporosis. However, treatment of osteoporosis is far from satisfactory due to poor adherence to existing medications and adverse reactions, there is an urgent to develop novel therapies for osteoporosis. Probucol, a synthetic compound with two characteristic phenolic rings, owns anti-inflammatory and antioxidant properties. Accumulating evidence have indicated that intracellular reactive oxygen species (ROS) is closely related to osteoclastogenesis. Hence, we investigated the potential effects of probucol on osteoclastogenesis in vivo and in vitro. In this study, TRAP staining and bone slice resorption assay showed that probucol suppressed RANKL-induced osteoclast formation and function. The mRNA and protein levels of osteoclastogenesis marker genes were reduced by probucol in a concentration-dependent manner. Besides, probucol suppressed osteoclast differentiation by inhibiting ROS production, MAPKs and NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of probucol on osteoclast formation and function. Consistent with the above findings, in vivo experiments demonstrated that probucol visibly alleviated bone loss caused by estrogen deficiency. In brief, these results showed the potential of anti-oxidant compound probucol in the treatment of osteoporosis, highlighting Nrf2 as a promising target in osteoclast-related disease.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis.

BACKGROUND: Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. OBJECTIVE: To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. METHODS: A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. RESULTS: Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1ß (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases. CONCLUSIONS: SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.

A Novel Role for RILP in Regulating Osteoclastogenesis and Bone Resorption.

Increased bone resorption caused by excessive number or activity of osteoclasts is the main cause of osteoporosis. Osteoclasts are multinucleated cells that are formed by the fusion of precursor cells. Although osteoclasts are primarily characterized by bone resorption, our understanding of the mechanisms that regulate the formation and function of osteoclasts is poor. Here we showed that the expression level of Rab interacting lysosomal protein (RILP) was strongly induced by receptor activator of NF-κB ligand in mouse bone marrow macrophages. Inhibition of RILP expression induced a drastic decrease in the number, size, F-actin ring formation of osteoclasts, and the expression level of osteoclast-related genes. Functionally, inhibition of RILP reduced the migration of preosteoclasts through PI3K-Akt signaling and suppressed bone resorption by inhibiting the secretion of lysosome cathepsin K. Treatments with siRNA-RILP attenuated pathologic bone loss in disease models induced by lipopolysaccharide. Thus, this work indicates that RILP plays an important role in the formation and bone resorption function of osteoclasts and may have a therapeutic potential to treat bone diseases caused by excessive or hyperactive osteoclasts.

Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction.

OBJECTIVES: Bone resorption of more conventional vascularized bone grafts have been well described showing minimal resorption over time. Few studies have evaluated osseous union and bone resorption in scapula tip free flaps (STFF) in the reconstruction of mandibulectomy defects. We aimed to describe our series on STFF with respect to osseous union and bone resorption over time. METHODS: Retrospective chart review of patients receiving STFF from January 2014-January 2017 (n = 25). A neuroradiologist analyzed follow-up CT scans to assess (1) STFF complete, partial, or no osseous union with native mandible and (2) STFF volume change over time in a subset with multiple follow-up scans (n = 18). RESULTS: Twenty-three of 25 patients (92%) showed complete or partial STFF osseous union with native mandible either distally or proximally. STFF volume change ranged from +4.8 to -54% (median -0.5%) over median follow-up interval of 23 months. History of chemoradiation therapy, bisphophonate use, sex, age, or smoking history did not correlate with bone resorption. CONCLUSIONS: STFFs shows high rates of osseous union and limited bone resorption that is equivalent to, or less than, vascularized fibular and iliac crest flaps. Clinically, this translates into both optimal healing and functional and cosmetic outcomes, especially in the setting of prior therapies. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2597-2602, 2023.