Bone Resorption In Patients Research Articles

Peri-implant Tissue Health and Bone Resorption in Implant- Supported Fixed Partial Rehabilitations.

To evaluate peri-implant tissue health and bone resorption in patients with implant-supported fixed partial rehabilitations. In particular, possible correlations between plaque accumulation and bone loss, as well as other periimplant health parameters, were investigated. A total of 44 patients rehabilitated with fixed implant-supported partial rehabilitations were included. The following parameters were recorded: spontaneous bleeding (SB), suppuration, bleeding on probing (BOP), plaque index (PI), and probing depth (PD). Periapical radiographs were taken to measure crestal bone loss (BL). A nonparametric test (Spearman rank coefficient; rs) was used to identify possible correlations between the clinical parameters recorded. A total of 121 implants were analyzed. Global PI and BOP were 49.58% and 20.25%, respectively. There were no cases of suppuration, and only 2 implants showed spontaneous bleeding. Mean BL was 1.53 mm (SD: 0.98). No implants showed peri-implantitis. There was a weak, statistically significant correlation between PI and BL (rs = 0.27, P [2-tailed] = .99) and between PI and the other peri-implant parameters (BOP: rs = 0.14, P = .14; PD: rs = 0.04, P = .65; SB: rs = -0.08, P = .34). A very weak correlation was also found between BL and BOP (rs = 0.1, P = .2) and between BL and PD (rs = 0.02, P = .7). Correlation was found between BL and age (rs = 0.13, P = .81) and between the other peri-implant parameters and age using dichotomization (> or < 65 years; PI: rs = -0.14, P = .11; PD: rs = -0.21, P = .01; BOP: rs = -0.21, P = .01; SB: rs = 0.05, P = .53). No statistically significant correlations were found between the clinical parameters evaluated and the sex or the dental arch treated (maxilla vs mandible). In contrast, the correlation between periodontal parameters and years elapsed since surgery (follow-up) was significant. The present research suggests that in implant-supported fixed partial rehabilitations, dental implants with greater plaque accumulation are more likely to present augmented probing depth, peri-implant inflammation, and bone loss, although the correlation is statistically very weak. Patient age and time of follow-up also significantly affected peri-implant health parameters.

IL-17A deficiency inhibits lung cancer-induced osteoclastogenesis by promoting apoptosis of osteoclast precursor cells.

Osteoclasts are crucial in the events leading to bone metastasis of lung cancer. Interleukin-17A (IL-17A) affects osteogenesis by regulating the survival of osteoclast precursors (OCPs) and is enriched in lung cancer cells. However, how factors derived from tumor cells that metastasize to bone affect osteoclastogenesis remains poorly understood. We examined whether IL-17A derived from lung cancer cells affects osteoclast differentiation by regulating OCP apoptosis. IL-17A expression was inhibited in A549 non-small cell lung cancer cells using RNA interference. Compared with conditioned medium (CM) from A549 cells (A549-CM), CM from IL-17A-deficient A549 cells (A549-si-CM) suppressed osteoclastogenesis. The mRNA expression of osteoclast-specific genes was downregulated following A549-si-CM treatment. Furthermore, A549-si-CM promoted osteoclast precursor apoptosis at an early stage of osteoclastogenesis, which was related to the promotion of caspase-3 expression by A549-si-CM during osteoclast differentiation. In vivo experiments also showed that inhibition of IL-17A expression in A549 cells reduced osteoclast activation and bone tissue destruction. Collectively, our results indicate that IL-17A deficiency inhibits lung cancer-induced osteoclast differentiation by promoting apoptosis of osteoclast precursors in the early stage of osteoclast formation and that IL-17A is a potential therapeutic target for cancer-associated bone resorption in patients with lung cancer.

Improvement of osteoblast adhesion, viability, and mineralization by restoring the cell cytoskeleton after bisphosphonate discontinuation in vitro.

Bisphosphonates are prescribed to treat excessive bone resorption in patients with osteoporosis. However, its use is associated with potential adverse effects such as medication-related osteonecrosis of the jaw, prompting the introduction of the drug holiday concept in patients prior to dentoalveolar surgery. Furthermore, bisphosphonate discontinuation has been studied in vivo, in humans, and in animal models. However, it is not known whether this approach could affect bone cells in vitro. Therefore, the objective of this study was to investigate the potential effects of bisphosphonate discontinuation on pre-osteoblast and osteoblast activities in vitro. Pre-osteoblasts (MC3T3) and osteoblasts were treated with bisphosphonate (alendronate) at concentrations of 1, 5, and 10 µM. Alendronate was then withdrawn at different time points. The negative control consisted of untreated cells (0 µM), while the positive control consisted of cells incubated with alendronate throughout the experiment. Cell viability, cell adhesion, cell cytoskeleton, mineralization, and gene expressions were investigated. Pre-osteoblasts and osteoblasts showed a decrease in cell viability after treatment with 5-10 μM alendronate for 4 days or longer. Two days of alendronate discontinuation significantly increased cell viability compared with the positive control. However, these levels did not reach those of the negative control. Bone nodule formation was reduced by alendronate. Discontinuation of alendronate regained bone nodule formation. Longer periods of discontinuation were more effective in restoring nodule formation than shorter periods. Addition of alendronate resulted in an increase in the percentage of dead cells, which, in turn, decreased when alendronate was discontinued. Alendronate affected the cell cytoskeleton by disassembling actin stress fibers. Cell adhesion and cell morphological parameters were also affected by alendronate. Discontinuation of alendronate restored cell adhesion and these parameters. Overall, the highest improvement after alendronate discontinuation was seen at 10 µM. However, alendronate treatment and discontinuation did not affect osteoblast gene expression. Discontinuation of alendronate helps to reverse the negative effects of the drug on cell viability, cell adhesion, and mineralization by restoring the cell cytoskeleton. Our data suggest the benefits of drug holiday and/or intermittent strategies for alendronate administration at the cellular level.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Acarbose diminishes postprandial suppression of bone resorption in patients with type 2 diabetes.

The alpha-glucosidase inhibitor acarbose is an antidiabetic drug delaying assimilation of carbohydrates and, thus, increasing the amount of carbohydrates in the distal parts of the intestines, which in turn increases circulating levels of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1). As GLP-1 may suppress bone resorption, acarbose has been proposed to potentiate meal-induced suppression of bone resorption. We investigated the effect of acarbose treatment on postprandial bone resorption in patients with type 2 diabetes and used the GLP-1 receptor antagonist exendin(9-39)NH2 to disclose contributory effect of acarbose-induced GLP-1 secretion. In a randomised, placebo-controlled, double-blind, crossover study, 15 participants with metformin-treated type 2 diabetes (2 women/13 men, age 71 (57-85years), BMI 29.7 (23.6-34.6kg/m2), HbA1c 48 (40-74mmol/mol)/6.5 (5.8-11.6%) (median and range)) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a six-week wash-out period. At the end of each period, circulating bone formation and resorption markers were assessed during two randomised 4-h liquid mixed meal tests (MMT) with infusions of exendin(9-39)NH2 and saline, respectively. Glucagon-like peptide 2 (GLP-2) was also assessed. Compared to placebo, acarbose impaired the MMT-induced suppression of CTX as assessed by baseline-subtracted area under curve (P=0.0037) and nadir of CTX (P=0.0128). During acarbose treatment, exendin(9-39)NH2 infusion lowered nadir of CTX compared to saline (P=0.0344). Neither parathyroid hormone or the bone formation marker procollagen 1 intact N-terminal propeptide were affected by acarbose or GLP-1 receptor antagonism. Acarbose treatment induced a greater postprandial GLP-2 response than placebo treatment (P=0.0479) and exendin(9-39)NH2 infusion exacerbated this (P=0.0002). In patients with type 2 diabetes, treatment with acarbose reduced postprandial suppression of bone resorption. Acarbose-induced GLP-1 secretion may contribute to this phenomenon as the impairment was partially reversed by GLP-1 receptor antagonism. Also, acarbose-induced reductions in other factors reducing bone resorption, e.g. glucose-dependent insulinotropic polypeptide, may contribute.

Influence of Platform-Switched Restoration on Bone Resorption in Patients Treated with Wide-Diameter, External-Hex-Connection Dental Implants: A 10-Year Follow-up Study.

Purpose: To investigate and assess the differences in crestal bone loss (CBL) between wide-diameter, external-hexagon-connection implants restored with platform-switching (PS) and platform-matching (PM) restorations with a follow-up of 10 years. Materials and Methods: This study retrospectively analyzed the updated and enlarged dataset of a 5-year prospective clinical study at 10-year follow-up. The data concerns 182 healthy adult subjects treated in a private dental practice who received a single wide-diameter implant with an external hexagon connection in the molar area, restored with either a PS restoration (test) or PM restoration (control). The amount of CBL was radiographically measured at each annual follow-up, as well as after 5 and 10 years of implant loading. In evaluating the association between the two types of abutments and bone loss (including change over time), a linear mixed effects model was run for longitudinal data. Results: Implants connected with PS restorations exhibited significantly lower reduction (0.25 mm) in CBL than those joined to PM restorations (P < .001; 95% CI from 0.22 to 0.29). However, both groups presented a higher increase in bone loss during the first year (0.58 mm in PS and 0.83 mm in PM) and a linear increment thereafter until the 10-year follow-up (0.046 mm/year; P < .001; 95% CI from .042 to .049). Conclusion: Notwithstanding the limitations of this study, it can be concluded that after 10 years of follow-up, the implant with a wide diameter and external-hexagon connection restored with a PS abutment seems to be more effective in reducing bone loss compared with the PM abutment.

OSTEOPOROSIS IN PATIENTS WITH COPD AND IMPACT ON QUALITY OF LIFE

Chronic obstructive pulmonary disease (COPD) is a progressive disease parenchyma destruction. Smoking is a major risk factor for this disease with frequent comorbidities. Osteoporosis is a common comorbidity in patients with COPD. Osteoporosis is characterized by lower bone density and changes in bone microarchitecture, leading to increased sensitivity and bone fractures occur. Fractures cause pain, further worsen already damaged pulmonary ventilation, reduced mobility and disability, and increased risk of thromboembolic disease, and even death. Osteoporosis in patients with COPD is probably evolving as the basis for both diseases there is systemic inflammation, but also because of the influence of inhaled tobacco smoke, reduced mobility of patients, vitamin D deficiency, lower body weight and older age. The use of systemic corticosteroids in the treatment of exacerbations of COPD increases the risk of developing osteoporosis. In addition, exacerbation of the intensification of inflammation, hypoxia and oxidative stress, as well as the imbalance between protease and anti-protease may contribute to increased bone resorption in patients with COPD. Osteoporosis can lead to kyphosis, which limits physical activity, leads to dyspnea, exacerbations and inadequate ventilation, which leads to a decrease in pulmonary function parameters. Osteoporosis can cause fractures that further limit movement, increasing the risk of thromboembolism and death. All of that have large impact on the quality of life COPD patients. Early prevention, timely diagnosis and treatment of osteoporosis are very important for patients with COPD. It is necessary significantly increase awareness of the connection between these two diseases.

Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study.

Peri-implant diseases are an emerging public health problem, and it's considered that limitations of standard diagnostics play the role herein. The study objective was the estimation of pathological bone resorption at clinical and biological level in patients with peri-implant mucositis (PIM) and peri-implantitis (PI) before and 6 months after standard treatment and to compare them with healthy controls (HC). The split-mouth interventional study included 60 patients affected with PIM or PI. Patients that also presented at least one more HC were enrolled in the study and underwent standard non-surgical and surgical treatment, respectively. Standard clinical parameters and soluble levels of RANKL were measured in peri-implant crevicular fluid baseline and 6 months following treatment. Clinical parameters and RANKL significantly decreased following treatment in PIM and PI. However, bleeding on probing and probing depth remained significantly increased when compared to HC. RANKL answered requests for biomarker of peri-implant diseases, its baseline levels were significantly increased in PIM and PI, they decreased following treatment and reached HC in peri-implantitis, while in PIM RANKL remained significantly increased. Presence of pathological bone resorption in patients lacked its clinical signs, and respective persistence following treatment suggest the need for biomarker-supported diagnosis for timely diagnosis of peri-implantitis and appropriate orientation of respective management strategies.

Bilateral resorption of mandibular angle in patient with systematic sclerosis - a case report

Progressive systemic sclerosis (PSS) is chronic autoimmune disease affecting a connective tissue. The symptoms of PSS in orofacial area are: restricted mouth opening, xerostomia, facial asymmetry and problems with oral hygiene. Radiographic images can show specific features like bone resorption, especially in mandibular region or periodontal ligament space widening. The aim of this study was to present the case of 56-year-old woman with characteristic scleroderma-related changes visible on panoramic radiograph. The patient diagnosed with severe systemic sclerosis was referred by dermatologist to general dentist. The woman experienced tightening of facial skin, xerostomia and reduced mouth opening which caused problems with daily oral hygiene and dental treatment. General dentist referred the patient to the Department of Dental and Maxillofacial Radiodiagnostics of Medical University of Lublin for the panoramic X-ray. One of the main findings was bilateral resorption of mandibular angles. Localization of the bone resorption in patients with scleroderma is related to attachements of masticatory muscles. Dentists and general doctors should be aware that some of the maxillofacial manifestations of systematic scleroderma can be visible on panoramic radiographs.

ODP130 Zoledronate-Induced Acute Tubular Necrosis With Baseline Normal Renal Function: A Rare Phenomenon

Abstract Introduction Zoledronate is an intravenous bisphosphonate that is commonly used to decrease bone resorption in patients with osteoporosis. The incidence of acute tubular necrosis (ATN) using zoledronate in patients with normal renal function is rare. Herein, we report the occurrence of severe ATN following treatment with a single zoledronate infusion in a patient with osteoporosis and normal renal function. Case Presentation A 51-year-old female with hypertension, well-controlled type 2 diabetes c/b gastroparesis without nephropathy(HbA1c6.8%), status-post hysterectomy, and bilateral oophorectomy, who was recently diagnosed with osteoporosis. Bone densitometry with Hologic revealed T scores of -2.8 at the spine and a T score of - 0.9 at the left hip. Her medications included lisinopril, metformin, and empagliflozin. Due to a history of gastroparesis, zoledronate was chosen as the preferred treatment. Pre-infusion blood work showed: a creatinine of 0.92 (0.5-1.1 mg/dl), 25-hydroxyvitamin-D 37.8 (30-100 NG/ml), calcium 8.9 (8.5-10.5mg/dl) and urine microalbumin 14 (&amp;lt;30 mg/g). Two days after the infusion, the patient developed emesis, diarrhea, oliguria, and fevers. She was evaluated in the emergency room and found to have acute renal failure (creatinine 10 mg/dL). She was given three liters of intravenous fluids with no improvement in urine output. Microscopic evaluation of spun urine revealed non-dysmorphic RBCs and numerous muddy brown granular casts consistent with ATN. Despite treatment with intravenous fluids, her creatinine did not improve and peaked on hospital days 11 to 11.65mg/dl. A 24-hour urine collection revealed proteinuria of 3 grams/24 hours. The patient was then empirically started on methylprednisolone 500mg for suspected glomerulonephritis. A renal biopsy was subsequently performed, which confirmed ATN. The patient's creatinine improved steadily to 5.49mg/dl by discharge. A subsequent creatinine one-month post-discharge was 1.36mg/dL. Discussion Zoledronate is widely used at low doses in the treatment of osteoporosis. ATN due to zoledronate infusion has been described in patients with pre-existing renal dysfunction and those receiving large and frequent doses for malignancy but rarely reported with the lower doses used to treat patients with osteoporosis and normal renal function. Zoledronate is believed to cause ATN by internalization in the renal tubular cells via the process of fluid-phase endocytosis. The intracellular accumulation of zoledronate may act as an epithelial toxin inducing tubular cytotoxicity. Interestingly, our patient had normal renal function without diabetic nephropathy and did not use nephrotoxic medications prior to the infusion. Conclusion We report a case of severe ATN due to a single dose of zoledronate in a patient with osteoporosis and previously normal renal function. This case highlights the need to be aware of the potential nephrotoxicity of zoledronate even in patients with normal renal function at baseline. Presentation: No date and time listed

Effect of phytate on hypercalciuria secondary to bone resorption in patients with urinary stones: pilot study

The objective is to evaluate the effect of phytate supplements on calciuria in patients with urinary stones and elevated bone resorption. The secondary objective is to analyze the therapeutic effect of phytate based on measurements of serum markers of bone resorption. This is a controlled randomized study included patients according to predefined inclusion and exclusion criteria, and randomized them into two groups. Patients in the phytate group received a 380 mg capsule of calcium-magnesium InsP6 (Salvat Laboratories®) every 24 h for 3 months and patients in the control group received no treatment. All included patients were male or female, 18–65 years old, had hypercalciuria (> 250 mg/24 h), had a ß-Crosslaps level greater than 0.4 ng/mL, and had bone densitometry results indicative of osteopenia or osteoporosis in the femur and/or spine. At study onset, calciuria was 321 ± 52 mg/24 h in the phytate group and 305 ± 57 mg/24 h in the control group (p > 0.05). At 3 months, calciuria was significantly lower in the phytate group than the control group (226 ± 45 mg/24 h vs. 304 ± 58 mg/24 h, p < 0.05). At study onset, the mean ß-CrossLaps level was 1.25 ± 0.72 ng/mL in the phytate group and 0.57 ± 0.13 ng/mL in the control group (p < 0.05). However, at 3 months, the ß-CrossLaps level was significantly lower in the phytate group than in the control group (0.57 ± 0.13 ng/mL vs. 0.77 ± 0.42 ng/mL, p < 0.05). Phytate reduced calciuria in patients with hypercalciuria secondary to bone resorption. The ß-CrossLaps assay was effective for evaluating the efficacy of phytate on hypercalciuria during follow-up.

Calprotectin and N-telopeptide of Type I Collagen (NTx) as Gingival Crevicular Fluid (GCF) Biomarker in Peri-Implantitis Patients

Introduction: Formulation of various preventive and therapeutic strategies is possible only by a better understanding of the immune-inflammatory profile of peri-implant diseases. For understanding the changes and turnover of bone, various markers have been used in the past literature, out of which, N-telopeptide of Type I Collagen (NTx) is acknowledged to be the most reliable marker.Aims and objectives: Assessment of calprotectin and NTx concentration in gingival crevicular fluid (GCF) around the implant sites in subjects suffering from peri-implantitis.Materials and methods: In total, 70 healthy individuals were included in the present study. These patients had opted for dental implants within the last decade. After collecting the peri-implant crevicular fluid (PICF) and GCF, various examinations were carried out. PICF samples were obtained with the help of sterile paper available in the form of strips. The enzyme-linked immunosorbent assay (ELISA) technique was used for measuring the calprotectin and NTx. All the readings were obtained in nanograms per microliter of PICF. All the results were recorded and analyzed.Results: The overall mean calprotectin and NTx values were observed to be in a significantly higher range within the sites suffering from peri-implantitis when compared with healthy locations. The calprotectin values and NTx levels were positively correlated with the mean values of periodontal parameters observed clinically.Conclusion: Both calprotectin and NTx could be used as a biomarker signifying the presence of inflammation as well as bone resorption in patients suffering from peri-implantitis.

The incidence of humeral bone resorption in uncemented reverse shoulder arthroplasty and the impact on functional outcomes

BackgroundFull-thickness bone resorption around the humeral stem in shoulder arthroplasty is an increasingly recognized phenomenon, but the impact on outcomes remains unclear. This study aims to investigate prevalence of bone resorption in patients with the Zimmer-Biomet Comprehensive reverse shoulder arthroplasty and the impact on the functional outcomes. MethodsA retrospective analysis was carried out on 65 consecutive patients with primary reverse total shoulder arthroplasty using the Comprehensive Shoulder System from 2014 to 2020, with a minimum of 12-month follow-up. The prevalence of humeral bone resorption was graded from 0 to 4, and risk factors for these changes and their impact on functional outcomes were further investigated. ResultsThe majority of patients (75%) were female with an average age of 75 years (53-93), with an overall average follow-up of 26 months (12-60). Bone resorption occurred in 53 patients (82%), and full-thickness bone resorption occurred in only 8 patients (12%). Metaphyseal bone (zones 1 and 7) is mostly at the risk of high-grade resorption. There was no difference in the final Oxford Shoulder Score between patients who had differential resorption grades from 0 to 4 (P = .5742). None of the risk factors from the previous literature including age, sex, indication for surgery, rotator cuff tear and repair, and intramedullary occupation ratio of the implant showed any impact on the rate of resorption. ConclusionFull-thickness humeral bone resorption occurred in approximately 12% of patients when using the Comprehensive reverse shoulder arthroplasty, but it has no impact on the functional outcomes or revision rate in the short-to-medium term.

A0919 - Effect of phytate on hypercalciuria secondary to bone resorption in patients with urinary stones

A0919 - Effect of phytate on hypercalciuria secondary to bone resorption in patients with urinary stones

Immunohistochemical features of the bone tissue of the lower extremities in patients with type 2 diabetes mellitus

Background: Diabetic neuroosteoarthropathy is a serious disabling complication of diabetes mellitus, which, in the absence of timely correct treatment, can lead to high amputations of the affected limb. At present, the reasons and mechanism of the development of Charcot’s foot are not completely clear. It is extremely important to determine the pathophysiological mechanisms of DNOAP formation and to search for reliable markers-predictors of this pathology.Aim: To study the immunohistochemical characteristics of the bone tissue of the lower extremities in patients with diabetic neuroosteoarthropathy in comparison with patients with diabetes mellitus without this pathology.Materials and methods: During the foot surgery, a bone fragment of the foot was harvested for immunohistochemical study of receptor markers for PINP, PIIINP, and RAGE in the group of patients with DNOAP compared with the control group.Results: The study included 20 patients with type 2 diabetes mellitus and were divided into 2 groups: 10 patients with DNOAP made up group 1, 10 patients without DNOAP — group 2.Patients in both groups were comparable in AGE, experience with type 2 diabetes, and glycemic control.During the immunohistochemical study, a significant increase in the staining intensity of receptor markers for PINP, PIIINP, and AGE was recorded in the group of patients with DNOAP compared with the control group (p &lt;0.05).Conclusion: For the first time, an immunohistochemical study of markers of bone resorption and AGE was carried out in persons with DNOAP. The results obtained indicate impaired collagen formation and, as a consequence, impaired bone formation and bone resorption in patients with DNOAP: in group 1, a statistically significant increase in the expression of PINP, PIIINP, and RAGE was revealed.

Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III

PurposePathogenic variants in GNPTAB and GNPTG, encoding different subunits of GlcNAc-1-phosphotransferase, cause mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma. This study aimed to investigate the cellular and molecular bases underlying skeletal abnormalities in patients with MLII and MLIII.MethodsWe analyzed bone biopsies from patients with MLIII alpha/beta or MLIII gamma by undecalcified histology and histomorphometry. The skeletal status of Gnptgkoand Gnptab-deficient mice was determined and complemented by biochemical analysis of primary Gnptgko bone cells. The clinical relevance of the mouse data was underscored by systematic urinary collagen crosslinks quantification in patients with MLII, MLIII alpha/beta, and MLIII gamma.ResultsThe analysis of iliac crest biopsies revealed that bone remodeling is impaired in patients with GNPTAB-associated MLIII alpha/beta but not with GNPTG-associated MLIII gamma. Opposed to Gnptab-deficient mice, skeletal remodeling is not affected in Gnptgko mice. Most importantly, patients with variants in GNPTAB but not in GNPTG exhibited increased bone resorption.ConclusionThe gene-specific impact on bone remodeling in human individuals and in mice proposes distinct molecular functions of the GlcNAc-1-phosphotransferase subunits in bone cells. We therefore appeal for the necessity to classify MLIII based on genetic in addition to clinical criteria to ensure appropriate therapy.

A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis.

The study was conducted to illustrate the effect of Romosozumab in postmenopausal osteoporosis patients. Romosozumab decreased the incidence of vertebral, nonvertebral, and clinical fractures significantly. In addition, decreased incidence of falls and increased bone mineral density at lumbar spine, total hip, and femoral neck was observed. Romosozumab is a monoclonal antibody that acts against the sclerostin pathway leading to enhanced bone formation and reduced bone resorption in patients with osteoporosis. Electronic search was performed on Medline (via PubMed), The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, till May 2020, for RCTs evaluating the effectiveness of Romosozumab in postmenopausal osteoporosis. RCTs evaluating the effect of Romosozumab on fractures and bone mineral density in postmenopausal osteoporosis patients. Meta-analysis was performed by Cochrane review manager 5 (RevMan) version 5.3. Cochrane risk of bias 2.0 tool and GRADE pro-GDT were applied for methodological quality and overall evidence quality, respectively. One hundred seventy-nine studies were screened, and 10 eligible studies were included in the analysis, with a total of 6137 patients in romosozumab group and 5732 patients in control group. Romosozumab significantly reduced the incidence of vertebral fractures [OR = 0.43 (95%CI = 0.35-0.52), High-quality evidence], nonvertebral fractures [OR = 0.78 (95%CI = 0.66-0.92), High quality], and clinical fractures [OR = 0.70 (95%CI = 0.60-0.82), High quality] at 24months. Significant reduction in incidence risk of falls [OR = 0.87 (95%CI = 0.78-0.96), High quality] was observed with romosozumab. Bone mineral density was significantly increased in the romosozumab treated groups at lumbar spine [MD = 12.66 (95%CI = 12.66-12.67), High quality], total hip [MD = 5.69 (95%CI = 5.68 - 5.69), Moderate quality], and femoral neck [MD = 5.18 (95%CI = 5.18-5.19), Moderate quality] at 12months. The total adverse events [RR = 0.98(95%CI = 0.96-1.01), Moderate quality] and serious adverse events [RR = 0.98(95%CI = 0.88-1.08), Moderate quality] with romosozumab were comparable to the control group. The current analysis with evidence on efficacy and safety of Romosozumab, authors opine to recommend the use of Romosozumab treatment for post-menopausal osteoporosis.Systematic review registration: PROSPERO registration number: CRD42019112196.

Dickkopf-1 perpetuated synovial fibroblast activation and synovial angiogenesis in rheumatoid arthritis.

Dickkopf-1 (Dkk-1), a regulatory molecule of the Wnt pathway, is elevated and leads to bone resorption in patients with RA. This study is aimed to investigate the contribution of Dkk-1 to synovial inflammation and synovial fibroblast-mediated angiogenesis in RA. The expression of Dkk-1 in RA synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF) was detected by real-time PCR and ELISA, respectively. RASF were stimulated with different pro-inflammatory factors. The expression of angiogenic factors, pro-inflammatory cytokines, and MMPs in RASF was analyzed by real-time PCR when Dkk-1 was inhibited or overexpressed. Meanwhile, the concentrations of MCP-1, IL-6, IL-8, and MMP-3 in the cell culture supernatant were assessed by ELISA. The effects of Dkk-1 on the MAPK signaling pathway were evaluated by western blot. Matrigel tube formation assay was employed to reveal the direct and indirect effects of Dkk-1 on synovial angiogenesis. Dkk-1 expression was elevated in synovial fluids and synovial fibroblasts of RA patients. Treatment with various pro-inflammatory cytokines significantly promoted DKK-1 expression in RASF. The production of potent angiogenic factors, pro-inflammatory cytokines, and MMPs in RASF was elevated, whereas the reverse results were found in the inhibitor groups. Silenced Dkk-1expression in RASF dampened capillary tube organization in both direct and indirect manners, resulting in restrained ERK, JNK, and p38 signaling pathway activation. We concluded that Dkk-1 exacerbated the inflammation, cartilage erosion, and angiogenesis mediated by synovial fibroblasts in RA. Modulation of DKK-1 expression may facilitate development of novel strategies to control RA. Key points • Dkk-1 expression was elevated in synovial fluids and synovial fibroblasts of RA patients. • Treatment with various pro-inflammatory cytokines significantly promoted DKK-1 expression. • Silenced Dkk-1expression in RASF dampened capillary tube organization.

Role of Urinary Calcium and Creatinine Ratio in Assessing Bone Resorption in Lepromatous Leprosy

Bony changes in lepromatous leprosy are one of the causes of deformity and disability. Fasting calcium and creatinine ratio in urine is used as a bone resorption marker in a number of diseases such as hyperthyroidism, osteoporosis, multiple myeloma, paget’s disease and sarcodosis. In lepromatous leprosy assessment of bone resorption might be done with that marker. To assess the role of fasting urinary calcium and creatinine ratio as a marker of bone resorption in patients with lepromatous leprosy. A case control study was conducted on 28 patients diagnosed as lepromatous leprosy and 28 age-matched healthy control. The participants who fulfilled all inclusion and exclusion criteria were studied by measuring fasting urinary calcium and creatinine level as well as observing X-rays of both hands and feet of affected individuals. The mean age of cases 38.1±14.2 years and 38.9±12.9 years was in control group. Male - female ratio was 3.6: 1. It was observed that 10.7% leprosy patients showed urinary Ca/Cr ratio &gt;0.20 (0.13±0.12) and 10.7% healthy control showed urinary Ca/Cr ratio ratio&gt;0.20 (mean ±SD 0.11±0.7). the difference was not statistically significant (p&gt;0.05). X-ray finding was positive in 14.3% leprosy patients and none of the control group. That difference was not significant statistically (p&gt;0.05). there was no relation between raised urinary Ca/Cr ratio and positive findings of bone resorption on x-rays among the leprosy cases.&#x0D; Bangladesh Med J. 2019 Sep; 48 (3): 28-33

Fracture Risk Reduction by Bisphosphonates in Mastocytosis?

Fragility fractures (FFxs) and osteoporosis are frequent manifestations of indolent systemic mastocytosis (ISM). So far, the effect of antiosteoporotic therapy on FFxs has scarcely been investigated. This study evaluates the long-term effect of bisphosphonate treatment on FFxs, bone mineral density (BMD), and bone resorption in patients with ISM in daily clinical practice. Patients with ISM who received bisphosphonates because of osteoporosis and/or FFxs were retrospectively analyzed (n= 58). Fractures were recorded by vertebral fracture assessment, X-rays of the thoracolumbar spine, medical records, and a questionnaire. Five-year analysis (n= 30) was made by comparing observed 5-year FFx risk with MastFx-predicted FFx risk for patients with ISM not treated with antiosteoporotic drugs and analyzing 5-year change in BMD and serum collagen C telopeptide (sCTx) Z-scores. During the median follow-up of 7.3 years, 14 of 58 patients suffered 40 FFxs. Five- and 10-year FFx-free survival were 81.9% (standard error [SE], 5.5%) and 67.0% (SE, 7.7%), respectively. FFx risk was significantly higher in patients with previous vertebral FFxs (P= .004), lower femoral BMD at baseline (P= .042), and history of anaphylaxis (P= .028). No 5-year FFx risk reduction could be proven, possibly due to the small sample size. The lumbar BMD Z-score significantly increased from median (interquartile range [IQR])-2.20 (-2.80 to-1.50) to-1.50 (-2.30 to-0.60) (P < .001, n= 27). The sCTx Z-score decreased from median 0.71 (IQR,-0.59 to 2.39) to-0.95 (-1.30 to-0.16) (P= .008, n= 15). Bisphosphonates significantly increase BMD and decrease sCTx in patients with ISM. However, FFxs still frequently occur. Especially patients with previous FFxs remain at high risk of new FFxs.