INDICATORS OF BONE METABOLISM IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH IMPAIRED BONE MINERAL DENSITY: CHARACTERISTICS, THEIR FEATURES AND DIAGNOSTIC VALUE.

Rheumatoid arthritis (RA) is an autoimmune disease with a chronic inflammatory process that affects bone metabolism and leading to impaired bone mineral density (BMD). Therefore, the determination of laboratory markers of bone metabolism contributes to a better understanding of the pathogenesis of metabolic bone diseases. The aim of the study - to characterize the bone metabolism parameters in rheumatoid arthritis patients with impaired bone mineral density, to find out their features and diagnostic value. The study included 76 patients randomly stratified by RA status who were treated in the Rheumatology Department of Lviv Regional Clinical Hospital, a municipal non-profit enterprise of Lviv Regional Council, from 2013 to 2019. The goal was achieved by performing three consecutive stages of the study. At the first stage, markers of bone formation and bone resorption were characterized. At the second stage, the peculiarities of these indicators were determined. The third stage was to determine the diagnostic value of the content of the markers of OCN formation, P1NP and resorption marker ß-CrossLaps. According to the results of the study at the first stage, it was found that, in RA patients with osteopenia, the serum content of markers of osteoblastic bone function OCN (p=0.000) and P1NP (p=0.035) was significantly lower compared to the healthy individuals of CG, while the content of the marker of bone resorption ß-CrossLaps was significantly higher (p=0. 021); in RA patients with OP, the serum content of both markers of osteoblastic bone function OCN (p=0.000) and P1NP (p=0.001) is significantly lower, while ß-CrossLaps (p>0.050) is only slightly higher compared to healthy CG subjects. According to the results obtained at the second stage of the study, it can be stated that the content of OCN and P1NP in the blood serum is significantly lower in RA patients both with osteopenia and OP compared to RA patients without BMD disorders. At the third stage of the study, it was found significant relationship between the content of P1NP and belonging to SG1 (AC -0.52). A confirmed relationship was found between the content of OCN and belonging to the group with OP (direct direction of AC 0.57; p=0.017). Bone structure disorders in rheumatoid arthritis patients with osteopenia are characterized by a weakening of bone formation and increased resorption processes; in rheumatoid arthritis patients with osteoporosis, the weakening of osteoblastic bone function is more pronounced compared to rheumatoid arthritis patients with osteopenia. For rheumatoid arthritis patients with unimpaired bone mineral density, the highest diagnostic value is provided by procollagen type I N-terminal propeptide. For rheumatoid arthritis patients with osteoporosis, osteocalcin is a diagnostically valuable marker.

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

C­X­C receptor 7 agonist acts as a C­X­C motif chemokine ligand 12 inhibitor to ameliorate osteoclastogenesis and bone resorption.

The C­X­C receptor (CXCR) 7 agonist, VUF11207, is a chemical compound that binds specifically to CXCR7, and negatively regulates C­X­C motif chemokine ligand 12 (CXCL12) and CXCR4­induced cellular events. Lipopolysaccharide (LPS) can induce inflammatory cytokines and pathological bone loss. LPS also induces expression of CXCL12, enhancing sensitivity to receptor activator of NF­κB ligand (RANKL) and tumor necrosis factor­α (TNF­α) in vivo. RANKL and TNF­α induce the differentiation of osteoclasts into osteoclast precursors and bone resorption. The current study was performed to examine the effects of a CXCR7 agonist on osteoclastogenesis and bone resorption induced by LPS in vivo. In addition, the mechanisms underlying these in vivo effects were investigated by in vitro experiments. Eight­week­old male C57BL/6J mice were subcutaneously injected over the calvariae with LPS alone or LPS and CXCR7 agonist. After sacrifice, the number of osteoclasts and the bone resorption area were measured. In vitro experiments were performed to investigate the effects of CXCL12 and CXCR7 agonist on osteoclastogenesis induced by RANKL and TNF­α. Mice injected with LPS and CXCR7 agonist showed significantly reduced osteoclastogenesis and bone resorption compared with mice injected with LPS alone. Moreover, the CXCR7 agonist inhibited CXCL12 enhancement of RANKL­ and TNF­α­induced osteoclastogenesis in vitro. Thus, CXCR7 agonist inhibited LPS­induced osteoclast­associated cytokines, such as RANKL and TNF­α, as well as RANKL­ and TNF­α­induced osteoclastogenesis in vitro by modulating CXCL12­mediated enhancement of osteoclastogenesis. In conclusion, CXCR7 agonist reduced CXCL12­mediated osteoclastogenesis and bone resorption.

Two-center validation of the Oulu resorption score for bone flap resorption after autologous cranioplasty.

OBJECTIVE: Autologous bone has been the gold standard of cranioplasty materials for decades. Unique to autologous cranioplasty, bone flap resorption is a poorly understood and unclearly defined complication. Even further, it has been unclear, whether the resorption process eventually stabilizes over time. Thus, the sufficient follow-up period after autologous cranioplasty is unknown. The Oulu Resorption Score (ORS) is a straight-forward classification system for the radiological interpretation of bone flap resorption. The aims of the present study were to evaluate the reliability of the ORS using intra-class correlation coefficient (ICC) and to assess the temporal progression of the resorption process. METHODS: We identified 108 consecutive autologous cranioplasty patients treated between 2005 and 2018 in two tertiary referral centers. All 365 head CT scans the patients had undergone were evaluated using the ORS in a blinded, independent two-center setting. Intra- and inter-observer reliabilities were calculated. The ORS was applied to study the temporal progression of the resorption process. RESULTS: The intra-observer reliability of the ORS was excellent (ICC 0.94, 95%CI 0.93-0.95). Inter-observer reliability was good-to-excellent (ICCs 0.87 and 0.89, 95%CIs 0.84-0.89 and 0.87-0.91, respectively). In scatterplot smoothing analyses, the progression of bone flap resorption appeared to stabilize 12-24 months after cranioplasty. CONCLUSIONS: ORS is the only validated radiological tool for the standardized analysis of bone flap resorption after autologous cranioplasty. Evaluated using the ORS, the resorption process seemed to stabilize during the first two postoperative years after cranioplasty, suggesting that the sufficient follow-up time after autologous cranioplasty is two years.

MicroRNAs in Peri-implant Crevicular Fluid Can Predict Peri-implant Bone Resorption: Clinical Trial with a 5-Year Follow-up.

PURPOSE: To evaluate the predictive value of microRNAs (miRNAs) found in peri-implant crevicular fluid (PICF) in the prognosis of peri-implant bone resorption. MATERIALS AND METHODS: Seven patients were rehabilitated with fixed partial dentures each supported by two dental implants (total of 14 implants). At 3 months post-implant insertion, a sample of peri-implant mucosa and a sample of PICF were taken at each implant site. MiRNAs were extracted from the samples and analyzed through microarray technology. MiRNAs extracted from PICF were compared with miRNAs extracted from soft peri-implant tissue and related with peri-implant bone resorption measured at the 5-year follow-up. RESULTS: During the 5-year follow-up, no dropouts and no implant failures were recorded. The mean bone resorption was 1.98 mm (median: 2 mm). Extracellular miRNAs were recovered in well-detectable amounts in all PICF samples. Specific miRNA expression profiles were predictive of bone resorption. Fourteen miRNAs that were altered in PICF in case of bone resorption were also altered in the soft peri-implant tissue of the same implant sites. CONCLUSION: MiRNAs may be used as biomarkers of peri-implant bone resorption, and their presence in PICF lays the foundations for the development of a noninvasive and site-specific liquid biopsy.

Intake of Docosahexaenoic Acid-Enriched Milk Beverage Prevents Age-Related Cognitive Decline and Decreases Serum Bone Resorption Marker Levels.

The pathogenic mechanism of dementia is still unknown, and the fundamental treatment remains to be established. Thus, there is growing interest in preventing dementia through diet. One of the functional ingredients attracting attention is docosahexaenoic acid. We conducted a 12-month, randomized, double-blind, placebo-controlled clinical trial in healthy elderly Japanese individuals with a Mini-Mental State Examination score of 28 or higher at baseline using a docosahexaenoic acid-enriched milk beverage containing 297 mg docosahexaenoic acid and 137 mg eicosapentaenoic acid. Consumption of a docosahexaenoic acid-enriched milk beverage increased the fatty acid levels of docosahexaenoic acid and eicosapentaenoic acid in erythrocyte membranes, which was the primary outcome of this study. Moreover, intake of this beverage prevented age-related cognitive decline and decreased serum bone resorption marker levels. Our data demonstrate that, even at a low dose, long-term daily intake of docosahexaenoic acid prevents dementia and may show beneficial effect on bone health.

Posicionamiento de implantes dentales simultáneos a la elevación de seno maxilar en rebordes con reabsorción severa / Dental implant placement simultaneous with maxillary sinus lifting on ridges with severe resorption

Introducción: El posicionamiento de implantes dentales simultáneos a la elevación de seno maxilar en rebordes con reabsorción severa < 4mm es una técnica quirúrgica sensible que disminuye los tiempos operatorios. Sin embargo, es considerada cirujano-dependiente y en caso de no darse el manejo adecuado puede generar complicaciones. Objetivo: Evaluar, luego de 24 meses de carga funcional, la estabilidad de los tejidos periimplantares del implante dental que se posicionó simultáneo a la elevación de seno maxilar en un reborde alveolar con reabsorción ósea severa < 4mm. Presentación de caso: Paciente masculino de 62 años con reabsorción ósea severa en zona de primer molar superior derecho. Luego de analizar los medios diagnósticos y la evidencia científica; se logró posicionar un implante dental simultáneo a la elevación de seno maxilar técnica de ventana lateral; cuatro meses después se realizó la segunda fase quirúrgica y finalmente fue rehabilitado con una corona en zirconio. Tuvo un periodo de seguimiento de 24 meses. Conclusiones: Un buen diagnóstico, manejo quirúrgico adecuado, la colaboración del paciente y los controles periódicos, resultan en una técnica segura, que proporciona estabilidad de los tejidos periimplantares(AU)

Introduction: Dental implant placement simultaneous with maxillary sinus lifting on ridges with severe resorption < 4 mm is a sensitive surgical technique that shortens the duration of interventions. However, it is considered to be operator dependent, and may cause complications if not appropriately managed. Objective: After 24 months of functional load, evaluate the stability of the peri-implant tissue of a dental implant placed simultaneously with maxillary sinus lifting on an alveolar ridge with severe bone resorption. Case presentation: A case is presented of a male 62-year-old patient with severe bone resorption in the area of the first upper right molar. Analysis of the diagnostic means and scientific evidence involved led to placement of a dental implant simultaneous with maxillary sinus lifting (lateral window technique). The second surgical stage was performed four months later. A zirconium crown was finally placed, and a 24-month follow-up period was started. Conclusions: With a good diagnosis, appropriate surgical management, patient cooperation and periodic controls, it is a safe technique that ensures the stability of peri-implant tissue(AU)

Effects of Mild and Moderate Monoclonal Antibody Dose on Inflammation, Bone Loss, and Activation of the Central Nervous System in a Female Collagen Antibody-induced Arthritis Mouse Model.

Induction of severe inflammatory arthritis in the collagen antibody-induced arthritis (CAIA) murine model causes extensive joint damage and pain-like behavior compromising analysis. While mild models are less severe, their reduced, variable penetrance makes assessment of treatment efficacy difficult. This study aimed to compare macroscopic and microscopic changes in the paws, along with central nervous system activation between a mild and moderate CAIA model. Balb/c mice (n=18) were allocated to control, mild, and moderate CAIA groups. Paw inflammation, bone volume (BV), and paw volume (PV) were assessed. Histologically, the front paws were assessed for joint inflammation, cartilage damage, and pre/osteoclast-like cells and the lumbar spinal cord and the periaqueductal gray (PAG) region of the brain for glial reactivity. A moderate CAIA dose induced (1) significantly greater local paw inflammation, inflammatory cell infiltration, and PV; (2) significantly more osteoclast-like cells on the bone surface and within the surrounding soft tissue; and (3) significantly greater glial reactivity within the PAG compared with the mild CAIA model. These findings support the use of a moderate CAIA model (higher dose of monoclonal antibodies with low-dose lipopolysaccharide) to induce more consistent histopathological features, without excessive joint destruction.

Osteosarcoma and Metastasis Associated Bone Degradation-A Tale of Osteoclast and Malignant Cell Cooperativity.

Cancer-induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer-dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast-mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast-mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer-associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer-associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.

Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model.

We describe the design and synthesis of OFS-1, an Osteoadsorptive Fluorogenic Sentinel imaging probe that is adsorbed by hydroxyapatite (HAp) and bone mineral surfaces, where it generates an external fluorescent signal in response to osteoclast-secreted cathepsin K (Ctsk). The probe consists of a bone-anchoring bisphosphonate moiety connected to a Förster resonance energy transfer (FRET) internally quenched fluorescent (IQF) dye pair, linked by a Ctsk peptide substrate, GHPGGPQG. Key structural features contributing to the effectiveness of OFS-1 were defined by structure-activity relationship (SAR) and modeling studies comparing OFS-1 with two cognates, OFS-2 and OFS-3. In solution or when preadsorbed on HAp, OFS-1 exhibited strong fluorescence when exposed to Ctsk (2.5-20 nM). Time-lapse photomicrographs obtained after seeding human osteoclasts onto HAp-coated well plates containing preadsorbed OFS-1 revealed bright fluorescence at the periphery of resorbing cells. OFS-1 administered systemically detected early osteolysis colocalized with orthotopic engraftment of RPMI-8226-Luc human multiple myeloma cells at a metastatic skeletal site in a humanized mouse model. OFS-1 is thus a promising new imaging tool for detecting abnormal bone resorption.

U.S. Montmorency Tart Cherry Juice Decreases Bone Resorption in Women Aged 65-80 Years.

Pre-clinical studies have demonstrated that tart cherries, rich in hydroxycinnamic acids and anthocyanins, protect against age-related and inflammation-induced bone loss. This study examined how daily consumption of Montmorency tart cherry juice (TC) alters biomarkers of bone metabolism in older women. Healthy women, aged 65-80 years (n = 27), were randomly assigned to consume ~240 mL (8 fl. oz.) of juice once (TC1X) or twice (TC2X) per day for 90 d. Dual-energy x-ray absorptiometry (DXA) scans were performed to determine bone density at baseline, and pre- and post-treatment serum biomarkers of bone formation and resorption, vitamin D, inflammation, and oxidative stress were assessed. Irrespective of osteoporosis risk, the bone resorption marker, tartrate resistant acid phosphatase type 5b, was significantly reduced with the TC2X dose compared to baseline, but not with the TC1X dose. In terms of indicators of bone formation and turnover, neither serum bone-specific alkaline phosphatase nor osteocalcin were altered. No changes in thiobarbituric acid reactive substances or high sensitivity C-reactive protein were observed in response to either TC1X or TC2X. We conclude that short-term supplementation with the higher dose of tart cherry juice decreased bone resorption from baseline without altering bone formation and turnover biomarkers in this cohort.

Long-term complications and implant survival rates after cranioplastic surgery: a single-center study of 392 patients.

Cranioplasty (CP) is a standard procedure in neurosurgical practice for patients after (decompressive) craniectomy. However, CP surgery is not standardized, is carried out in different ways, and is associated with considerable complication rates. Here, we report our experiences with the use of different CP materials and analyze long-term complications and implant survival rates. We retrospectively studied patients who underwent CP surgery at our institution between 2004 and 2014. Binary logistic regression analysis was performed in order to identify risk factors for the development of complications. Kaplan-Meier analysis was used to estimate implant survival rates. A total of 392 patients (182 females, 210 males) with a mean age of 48 years were included. These patients underwent a total of 508 CP surgeries. The overall complication rate of primary CP was 33.2%, due to bone resorption/loosening (14.6%) and graft infection (7.9%) with a mean implant survival of 120 ± 5 months. Binary logistic regression analysis showed that young age (< 30 years) (p = 0.026, OR 3.150), the presence of multidrug-resistant bacteria (p = 0.045, OR 2.273), and cerebrospinal fluid (CSF) shunt (p = 0.001, OR 3.137) were risk factors for postoperative complications. The use of titanium miniplates for CP fixation was associated with reduced complication rates and bone flap osteolysis as well as longer implant survival rates. The present study highlights the risk profile of CP surgery. Young age (< 30 years) and shunt-dependent hydrocephalus are associated with postoperative complications especially due to bone flap autolysis. Furthermore, a rigid CP fixation seems to play a crucial role in reducing complication rates.

TNFα inhibitors reduce bone loss in rheumatoid arthritis independent of clinical response by reducing osteoclast precursors and IL-20.

OBJECTIVES: About half of RA patients treated with TNFα inhibitors either do not respond or lose their initial therapeutic response over time. The clinical response is measured by reduction in DAS28, which primarily reflects inflammation. However, other effects of TNFα inhibitors, such as impact on bone erosion, are not assessed by DAS28. We aimed to examine the effect of TNFα inhibitors on bone density, bone biomarkers and cytokine production in responder and non-responder patients and assessed mechanisms of action. METHODS: BMD in the lumbar spine and femur neck of 117 RA patients was measured by DEXA scan. Bone turnover biomarkers CTX, osteoprotegerin (OPG), osteocalcin and RANKL were measured by ELISA. Levels of 16 cytokines in plasma and in tissue culture supernatants of ex vivo T cells were measured by multiplex assays and ELISA. The effect of treatment with TNFα inhibitors on blood mononuclear cell (MNC) differentiation to osteoclast precursors (OCP) was measured flow cytometry and microscopy. RESULTS: TNFα inhibitors improved lumbar spine BMD but had modest effects on blood bone biomarkers, irrespective of patients' clinical response. Blood OCP numbers and the ability of monocytes to differentiate to OCP in vitro declined after treatment. Treatment also reduced RANK expression and IL-20 production. BMD improvement correlated with reduced levels of IL-20 in responder patients. CONCLUSION: This study reveals that TNFα inhibitors reduce lumbar spine bone loss in RA patients irrespective of changes in DAS28. The reduction in bone loss is associated with reduction in IL-20 levels in responder patients.

A Window Into the Whole Story: Temporal Bone Plasmacytoma Presenting With a Mobile Third Window.

A 63-year-old man presented with imbalance when coughing due to a respiratory tract infection. He had a history of multiple myeloma with a plasmacytoma of the left temporal bone. Examination revealed a positive leftward head impulse test, no spontaneous nystagmus, left-beating positional nystagmus, and left-beating Valsalva-induced nystagmus. Videonystagmography, audiology, and comprehensive vestibular function tests revealed a subtotal left peripheral audio-vestibular loss. Temporal bone computed tomography showed an unchanged bony erosion of the left labyrinth from 2 years prior. Vertigo subsided after treatment of the respiratory tract infection. Although no tumor progression was evident, coughing had triggered a preexisting third mobile window to declare itself. Laryngoscope, 131:E966-E969, 2021.

Risk Factors for Recurrence After Arthroscopic Instability Repair-The Importance of Glenoid Bone Loss >15%, Patient Age, and Duration of Symptoms: A Matched Cohort Analysis.

BACKGROUND: Glenoid bone loss (GBL) has been implicated as a risk factor for failure of arthroscopic anterior glenohumeral instability repair. Although certain amounts of GBL are associated with higher recurrence rates, there are limited studies on successes versus failures in these cohorts. PURPOSE: To compare the outcomes of arthroscopic Bankart repair in patients with and without GBL to determine a threshold percentage of GBL that predicts success. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: All consecutive patients who underwent arthroscopic Bankart repair for anterior shoulder instability between 2004 and 2013 were prospectively enrolled. Patients with ≤25% GBL were included. Patients with no GBL were grouped and compared with those having 5% to 25% GBL. Outcomes included Single Assessment Numerical Evaluation, Western Ontario Shoulder Index, and American Shoulder and Elbow Surgeons scores, with evidence of recurrent instability. Patients with and without GBL were statistically compared with respect to outcomes and recurrence rates. RESULTS: Of 434 eligible patients, the cases of 405 (45 female, 360 male; mean age, 27.5 years [range, 18-47 years]) were followed for a mean 61 months (range, 48-96 months). There were 189 (46.6%) with no GBL and 216 (53.3%) with GBL; the mean GBL of the latter cohort was 15% (range, 5%-25%). The mean duration of instability symptoms was 7.9 months (range, 1-21 months) and was significantly longer in the GBL group (P < .05). The mean recurrence rate was 14.8%, which was significantly greater in patients presenting with GBL versus those with none (48/216 [22.2%] vs 12/189 [6.3%]; P < .01). Within the GBL group, GBL ≥15%, duration of symptoms >5 months, and younger age (<20 years) were independent risk factors for failure (P < .01). Patients with any GBL had >4-times greater odds of recurrence after arthroscopic stabilization (odds ratio, 4.21; 95% CI, 2.16-8.21). Moreover, patients presenting for arthroscopic Bankart repair with GBL ≥15% had nearly 3-times greater odds of recurrent instability. CONCLUSION: GBL ≥15% in an active patient population portends to increased odds of recurrent instability events and inferior clinical outcomes after arthroscopic Bankart repair. Furthermore, nonmodifiable risk factors, such as age (<20 years) and duration of symptoms before presentation (>5 months), significantly affect risk of recurrence and should be key factors when counseling patients on risk of failure and determining the ideal procedure for the individual patient.

Cup-on-cup technique: a reliable management solution for severe acetabular bone loss in revision total hip replacement.

BACKGROUND: The management of acetabular bone loss is a challenging problem in revision total hip arthroplasty (rTHA). The goals of treatment are a stable acetabular fixation, implant stability, and restoration of hip centre of rotation.This study aims to report clinical, radiological outcomes and complications at short-term to mid-term follow-up of the cup-on-cup technique in the management of severe acetabular bone loss in rTHA. METHODS: We retrospectively reviewed the records of patient receiving rTHA performed with double porous tantalum cup technique in a single Joint Replacement Unit from 2014 to 2017. Objective and subjective clinical scores (Harris Hip Score, Oxford Hip Score, and visual analogue scale), radiological parameters (centre of rotation, leg-length discrepancy, heterotopic ossification, osseointegration, loosening and radiolucencies) and complications were recorded. We analysed the implant survival rate and periprosthetic joint infection rate. RESULTS: We included 9 patients (9 hips) with a mean follow-up of 35.3 ± 10.8 months. Functional scores showed a statistically significant improvement at the final follow-up (p < 0.01). All patients rated their surgery as satisfactory. The cup-on-cup construct demonstrated radiological osseointegration with the centre of rotation restoration and leg length discrepancy improvement. In 1 patient, periprosthetic joint infection was diagnosed and treated with suppressive antibiotic therapy. No patients underwent acetabular components revision surgery for any reason. CONCLUSIONS: Cup-on-cup technique is a valid and safe solution for reconstruction of selected Paprosky type IIIA and IIIB bone defects with satisfactory clinical and radiographic results at short-term and mid-term follow-up.

An Acid-Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities.

A rationally designed pH-activatable fluorescent probe (pHocas-RIS) has been used to measure localised pH levels in osteocytic lacunae in bone tissue. Conjugation of the moderate bone-binding drug risedronate to a pH-activatable BODIPY fluorophore enables the probe to penetrate osteocytic lacunae cavities that are embedded deep within the bone matrix. After injection of pHocas-RIS, any osteocytic lacunae caused by bone-resorbing osteocytes cause the probe to fluoresce in vivo, thus allowing imaging by intravital two-photon excitation microscopy. This pH responsive probe enabled the visualization of the bone mineralizing activities of acid producing osteocytes in real time, thus allowing the study of their central role in remodeling the bone-matrix in healthy and disease states.

Unexpected Bone Resorption in Mentum Induced by the Soft-Tissue Filler Hyaluronic Acid: A Preliminary Retrospective Cohort Study of Asian Patients.

BACKGROUND: As one of the most commonly used soft-tissue fillers, hyaluronic acid is generally considered safe and efficacious. However, evident bone resorption in mentum was observed. In this study, the authors analyzed the impact of hyaluronic acid on bone resorption in mentum and the influencing factors. METHODS: The authors retrospectively compared the computed tomographic scans of patients with or without mentum augmentation using hyaluronic acid. The body mass index- and sex-matched control group was selected randomly. Semimandibular bone resorption index was calculated as the ratio of bone thickness in the incisive fossa to that in the mandibular symphysis. Injection volume, injection interval, the number of injections, product, complication were also recorded. RESULTS: From January of 2014 to June of 2019, 80 patients (160 cases) and 80 controls were recruited. The bone resorption index in the hyaluronic acid injection cohort was significantly lower than in the controls (75.25 ± 10.02 versus 82.86 ± 6.38; p = 0.000). Patients injected with greater than or equal to 1 ml per time were more susceptible to bone erosion compared with patients injected with less (68.89 ± 10.84 versus 76.49 ± 9.42; p = 0.000). There was no significant difference between one- versus multiple-injection groups and short-injection-interval versus long-injection-interval (≥6 months) groups. Furthermore, no reduced aesthetics were realized. CONCLUSIONS: Hyaluronic acid injection could induce bone resorption in the mentum; nevertheless, the aesthetics were not impaired. The severity of the bone loss was positively correlated with the injection volume per time; therefore, large-volume injection of hyaluronic acid should be performed with caution. The patients should be fully informed about this complication preoperatively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

A phase 1 pooled PK/PD analysis of bone resorption biomarkers for odanacatib, a Cathepsin K inhibitor.

To develop a framework for evaluating the resorption effects of Cathepsin K (CatK) inhibitors and to inform dose regimen selection, a pharmacokinetic/pharmacodynamic (PK/PD) model for odanacatib (ODN) was developed based upon data from Phase 1 studies. Pooled PK/PD data from 11 studies (N = 249) were fit reasonably to a population inhibitory sigmoid Emax model. Body weight on E0 (baseline uNTx/Cr, urinary N-terminal telopeptide normalized by creatinine) and age on Emax (fractional inhibition of the biomarker response) were significant covariates for biomarker response. Simulations of typical osteoporosis patients (by age, sex and weight) indicated minimal differences between sexes in concentration-uNTx/Cr relationship. There was no evidence that regimen (daily vs. weekly dosing) influenced the PK/PD relationship of resorption inhibition for odanacatib. PK/PD models based on data from odanacatib (ODN) Phase 1 studies demonstrated that uNTx/Cr was an appropriate bone resorption biomarker for assessment of the effects of a CatK inhibitor. The models also identified the determinants of response in the PK/PD relationship for ODN (body weight on E0 and age on Emax).

Evaluation of PRF Efficiency in the Treatment of Infrabony Defects.

AIM: The present study aimed to investigate the effectiveness of PRF in the treatment of infrabony defects in patients with chronic periodontitis by evaluating the clinical outcome through periodontal depth, clinical attachment level at the baseline, 6 and 9 months post operatively. MATERIAL AND METHODS: Sixty infrabony defects with probing depth ≥ 5 mm were treated. The inclusion criterion was the necessity for surgical bilateral maxillary treatment. By using split-mouth study design, each patient had one side treated with conventional flap surgery and the other side with conventional flap surgery and PRF. Clinical parameters, such as probing depth (PD) and clinical attachment lost (CAL), were recorded in both groups at baseline, 6 and 9 months post operatively. RESULTS: Positive effects for all clinical and radiographic parameters were evident in the group with PRF. Mean PD reduction demonstrated statistically significant greater results in the test group (4.00±1.07 mm) compared to the control one (4.83±0.99 mm), p = 0.003 after 9 months postoperatively. After 9 months, there were better results in the test group compared to the control group for CAL (5.60±1.61 mm, 6.20±1.58 mm), but statistically not significant. CONCLUSION: Additional use of PRF in the conventional surgical treatment of infrabony defects demonstrated better parameters than the open flap debridement alone.