Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles.

BACKGROUND: Wear particles-induced osteolysis is a major long-term complication after total joint arthroplasty. Up to now, there is no effective treatment for wear particles-induced osteolysis except for the revision surgery, which is a heavy psychological and economic burden to patients. A metabolite of gut microbiota, short chain fatty acids (SCFAs), has been reported to be beneficial for many chronic inflammatory diseases. This study aimed to investigate the therapeutic effect of SCFAs on osteolysis. METHODS: A model of inflammatory osteolysis was established by applying CoCrMo alloy particles to mouse calvarium. After two weeks of intervention, the anti-inflammatory effects of SCFAs on wear particle-induced osteolysis were evaluated by Micro-CT analysis and immunohistochemistry staining. In vitro study, lipopolysaccharide (LPS) primed bone marrow-derived macrophages (BMDMs) and Tohoku Hospital Pediatrics-1 (THP-1) macrophages were stimulated with CoCrMo particles to activate inflammasome in the presence of acetate (C2), propionate (C3), and butyrate (C4). Western blotting, Enzyme-linked immunosorbent assay, and immunofluorescence were used to detect the activation of NLRP3 inflammasome. The effects of SCFAs on osteoclasts were evaluate by qRT-PCR, Western blotting, immunofluorescence, and tartrate-resistant acid phosphatase (TRAP) staining. Additionally, histone deacetylase (HDAC) inhibitors, agonists of GPR41, GPR43, and GPR109A were applied to confirm the underlying mechanism of SCFAs on the inflammasome activation of macrophages and osteoclastogenesis. RESULTS: C3 and C4 but not C2 could alleviate wear particles-induced osteolysis with fewer bone erosion pits (P < 0.001), higher level of bone volume to tissue volume (BV/TV, P < 0.001), bone mineral density (BMD, P < 0.001), and a lower total porosity (P < 0.001). C3 and C4 prevented CoCrMo alloy particles-induced ASC speck formation and nucleation-induced oligomerization, suppressing the cleavage of caspase-1 (P < 0.05) and IL-1ß (P < 0.05) stimulated by CoCrMo alloy particles. C3 and C4 also inhibited the generation of Gasdermin D-N-terminal fragment (GSDMD-NT) to regulate pyroptosis. Besides, C3 and C4 have a negative impact on osteoclast differentiation (P < 0.05) and its function (P < 0.05), affecting the podosome arrangement and morphologically normal podosome belts formation. CONCLUSION: Our work showed that C3 and C4 are qualified candidates for the treatment of wear particle-induced osteolysis.

A case of bone destruction caused by chronic non-bacterial osteomyelitis (CNO) successfully repaired with a tumour necrosis factor-α (TNF-α) inhibitor, adalimumab.

Chronic Non-bacterial Osteomyelitis (CNO) is an autoinflammatory bone disorder that causes non-bacterial and non-neoplastic osteomyelitis. CNO appeared to the long bone, clavicle, pelvis, and spine on children commonly. This time, we report a case with osteomyelitis of the mandible for the adult-onset. A 25-year-old woman presented pustulosis palmaris/pustular psoriasis after the extraction of the lower right tooth 1 year before hospitalisation. She felt pain and swelling of the right jaw and an antibiotic, NSAIDs, and glucocorticoids were ineffective. The cortical osteotomy of right mandibular bone was carried out 2 months before hospitalisation, but the symptom was not improved and she was admitted to our hospital. For pustular psoriasis with CNO, we treated her with adalimumab and the pain and swelling in her right jaw disappeared immediately. One and two years after the treatment, osteolytic and sclerotic bone lesion and osteomyelitis were improved in both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). An anti-TNF-α antibody may be an effective therapy for CNO resistant to conventional treatment.

Bone microarchitecture deteriorations and a fragility fracture in a patient with beta and alpha heterozygous thalassemia: a case report.

To date there are few studies that have investigated bone mineral density (BMD) and markers of bone metabolism in patients with thalassemia minor form. None of the previous trials presented bone structure analysis in the patient populations. We present the case of a 24-year-old Turkish woman with heterozygous beta and alpha thalassemia who sustained a low-trauma fracture of the inferior pubic ramus. Despite normal markers of bone metabolism, the dual X­ray absorptiometry (DXA) showed decreased areal bone mineral density. Furthermore, severely reduced bone structure parameters and reduced volumetric bone mineral density was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Due to these diagnostic findings at time of peak bone mass, an osteoanabolic therapy with teriparatide for 24 months was initiated. The findings concerning BMD and bone structure in this patient can be seen as caused by the beta and alpha thalassemia.

Managing bone loss in revision total hip arthroplasty: the acetabulum.

Osteolysis is the greatest threat to the viability of modern acetabular implants. The etiology and natural history of osteolysis remain unknown. Patients with cementless implants who have osteolysis are challenging to treat. There are no standards for follow-up methods or frequency, and there is little evidence to support timing of the decision to begin treatment in these patients. The natural history of proposed treatment options is also unknown. Reconstruction of the acetabulum in the presence of bone loss is difficult. Classifications have been developed to guide management. Multiple options exist for revision acetabular surgery, and it is important to understand the rationale and data in support of these options. A review of the literature was undertaken and algorithms were developed to help address acetabular bone loss in patients undergoing revision surgery.

Treatment of Paget's disease of bone with alendronate.

In summary, the clinical efficacy studies provide clear evidence that treatment with oral alendronate markedly suppresses bone turnover and produces clinical improvement in pagetic patients. Serum alkaline phosphatase was greatly decreased by treatment, and the response to alendronate was superior to that observed for currently available therapies such as etidronate and calcitonin, which usually reduce alkaline phosphatase, on average, by 40%-50%. Alendronate also markedly reduced urinary resorption markers and induced radiologic improvement of pagetic osteolysis. A majority of alendronate-treated patients normalized their serum alkaline phosphatase by month 6. This observation is likely to be relevant to the duration of response to treatment, as previous studies have shown that the degree of suppression of alkaline phosphatase after antiresorptive treatment correlates with the duration of remission. Therefore, patients who responded to treatment with alendronate, especially those who normalized their alkaline phosphatase levels, are likely to maintain the biochemical remission for several years. Indeed, preliminary unpublished data seem to indicate that alendronate is capable of producing long-term biochemical remission in the majority of patients. In addition to its efficacy, the safety and tolerability profile of alendronate 40 mg/day was very favorable and, overall, comparable to that of placebo.

[Biosphonates in oncology]. / Les bisphosphonates en cancérologie.

MECHANISM OF ACTION: Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Bisphosphonates inhibit bone resorption by reducing osteoclastic activity. INDICATIONS: Bisphosphonates were shown to be effective in treating cancer-related hypercalcemia. Recent large randomized clinical trials have shown the efficacy of bisphosphonates in reducing bone pain, pathological fractures and spinal cord compression for patients with multiple myeloma and breast cancer metastatic to bone. The potential survival benefit from pamidronate in patients with advanced myeloma warrants further study. FUTURE: Future clinical trials will use more potent bisphosphonates (zoledronate, ibandronate) with the ultimate goal of trying to prevent bone metastases.

Paget disease: when to treat and when not to treat.

Paget disease of bone is a focal disorder of the skeleton that can affect one or more bones. Many patients are discovered accidentally because of elevated serum alkaline phosphatase activity or an abnormal skeletal radiograph intended to evaluate an unrelated condition. Patients are often asymptomatic, but a subset experience considerable morbidity that can include bone pain and skeletal deformity, as well as a variety of regional complications, such as hearing loss associated with cranial involvement, degenerative arthritis of the hip or knee, fractures of the lower extremities and, rarely, sarcoma or giant cell tumors. Bisphosphonates have proven to be effective in controlling disease activity because they inhibit osteoclast function. Administration of these agents can relieve bone pain, decrease biochemical markers of bone resorption and bone formation, and retard or reverse the early osteolytic phase of the disease. Future studies are needed to determine whether these drugs, if used in an early stage of the disease, can prevent complications in asymptomatic patients.

[Periprosthetic osteolysis following the total hip arthroplasty].

The periprosthetic osteolysis is one of the complications of artificial joint replacement. The function and the stability of the hip joint will be severely affected once the periprosthetic osteolysis occurred postoperatively,so it's necessary to fully recognize the mechanism of the osteolysis. There is no globally accepted diagnostic standard of this disease, and then, the grading of the postoperative hip joint function is indispensable. The using of diphosphonate to prevent the osteolysis has positive significance, but it is not broadly used in clinical. Taking the periprosthetic osteolysis of hip arthroplasty as the central, this article shows a briefly overview of this subject.