Long-Term Ligature-Induced Periodontitis Exacerbates Development of Bisphosphonate-Related Osteonecrosis of the Jaw in Mice.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a detrimental intraoral lesion that occurs in patients with long-term or high-dose use of anti-resorptive agents such as bisphosphonates. Tooth extraction is a known risk factor for BRONJ, and such intervention is often performed to eliminate existing pathological inflammatory conditions. Previously, we determined that ligature-induced periodontitis (LIP) is a risk factor for the development of osteonecrosis in mice, but it remains unclear whether the chronicity of LIP followed by extraction influences osteonecrosis development. In this study, we assess the effect of short-term and long-term LIP (ligature placed for 3 weeks [S-LIP] or 10 weeks [L-LIP], respectively) on osteonecrosis development in mice receiving 250 µg/kg/week zoledronic acid (ZOL). When compared to S-LIP, L-LIP caused 70% (p ≤ 0.0014) more bone loss without altering microbe composition. In the presence of ZOL, bone loss mediated by LIP was prevented and bone necrosis was induced. When the ligated tooth was extracted, histologic hallmarks of osteonecrosis including empty lacunae and necrotic bone were increased by 88% (p = 0.0374) and 114% (p = 0.0457), respectively, in L-LIP compared to S-LIP. We also observed significant increases in serum platelet factor 4 (PF4) and macrophage inflammatory factor 1 γ (MIP1γ) in mice that received ZOL treatment and had tooth extractions compared to controls, which may be systemic markers of inflammation-associated osteonecrosis development. Additionally, CD3+ T cells were identified as the major immune population in both health and disease, and we observed a 116% (p = 0.0402) increase in CD3+IL23R+ T cells in L-LIP compared to S-LIP lesions following extraction. Taken together, our study reveals that extracting a periodontally compromised tooth increases the formation of necrotic bone compared to extracting a periodontally healthy tooth and that osteonecrosis may be associated with the duration of the preexisting pathological inflammatory conditions. © 2022 American Society for Bone and Mineral Research (ASBMR).

Juvenile-onset multifocal osteonecrosis in systemic lupus erythematosus: A case report.

RATIONALE: Osteonecrosis (ON) is a devastating illness that leads to bone ischemia and potential joint destruction. Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, with multi-system involvement which is closely associated with occurrence of ON. Multifocal ON, with an estimated morbidity of 3% in SLE patients, is extremely rare in juvenile subjects. PATIENT CONCERNS: A 13.3-year-old female SLE patient was admitted to hospital 20 months following the SLE diagnosis because of a sudden aggravation of sore knees. She suffered from double knee joint pain and her left knee joint showed typical signs of inflammation including redness, swelling, heat, and pain. DIAGNOSES: The SLE patient was diagnosed with multifocal ON of her knee joint based on magnetic resonance imaging findings of bone destruction and osteoproliferation at the bilateral distal femur and proximal tibia. INTERVENTIONS: The patient received high-dose methylprednisolone and intravenous cyclophosphamide pulse therapies for controlling active lupus and nephritis. Oral calcitriol and dipyridamole were administered to alleviate knee pain and inhibit thrombi formation, thereby suppressing ON progress. OUTCOMES: Three weeks following the treatment, the swelling in patient's left knee subsided. Her self-reporting pain score decreased from 9 to 4 and walking time increased from 45minutes to 90minutes per day. Nearly 5 weeks later, the pain in bilateral knee joints disappeared and the patient could walk without difficulties. LESSONS: This patient is the youngest SLE patient who developed multifocal ON based on the reported literature. It suggests that ON can occur in young SLE patients. A combination of internal and external risk factors can promote the development of ON. The balanced approach to the application of corticosteroids and immunosuppressors in the treatment of SLE and prevention of ON is a challenging problem that deserves further exploration.

An underlying diagnosis of osteonecrosis of bone is associated with worse outcomes than osteoarthritis after total hip arthroplasty.

BACKGROUND: Well-designed studies of complications and readmission rates in patients undergoing total hip arthroplasty (THA) with osteonecrosis are lacking. Our objective was to examine if a diagnosis of osteonecrosis was associated with complications, mortality and readmission rates after THA. METHODS: We analyzed prospectively collected data from an integrated healthcare system's Total Joint Replacement Registry of adults with osteonecrosis vs. osteoarthritis (OA) undergoing unilateral primary THA during 2001-2012, in an observational cohort study. We examined mortality (90-day), revision (ever), deep (1 year) and superficial (30-day) surgical site infection (SSI), venous thromboembolism (VTE, 90-day), and unplanned readmission (90-day). Age, gender, race, body mass index, American Society of Anesthesiologists class, and diabetes were evaluated as confounders. We used logistic or Cox regression to calculate odds or hazard ratios (OR, HR) with 95% confidence intervals (CI). RESULTS: Of the 47,523 primary THA cases, 45,252 (95.2%) had OA, and 2,271 (4.8%) had osteonecrosis. Compared to the OA, patients with osteonecrosis were younger (median age 55 vs. 67 years), and were less likely to be female (42.5% vs. 58.3%) or White (59.8% vs. 77.4%). Compared to the OA, the osteonecrosis cohort had higher crude incidence of 90-day mortality (0.7% vs. 0.3%), SSI (1.2% vs. 0.8%), unplanned readmission (9.6% vs. 5.2%) and revision (3.1% vs. 2.4%). After multivariable-adjustment, patients with osteonecrosis had a higher odds/hazard of mortality (OR: 2.48; 95% CI:1.31-4.72), SSI (OR: 1.67, 95%CI:1.11-2.51), unplanned 90-day readmissions (OR: 2.20; 95% CI:1.67-2.91) and a trend towards higher revision rate 1-year post-THA (HR: 1.32; 95% CI: 0.94-1.84), than OA patients. CONCLUSIONS: Compared to OA, a diagnosis of osteonecrosis was associated with worse outcomes post-THA. A detailed preoperative discussion including the risk of complications is needed for informed consent from patients with osteonecrosis.

[Study on the Distribution of Constitutions of Chinese Medicine in Patients with Osteonecrosis of Femoral Head].

OBJECTIVE: To observe the distribution of constitution types of Chinese medicine (CM) in patients with osteonecrosis of femoral head (ONFH). METHODS: Totally 130 ONFH patients were recruited. Constitution types of CM were identified in all patients. Distribution features of constitution types of CM in ONFH patients were observed. The differences of distribution in gender, age, single or bilateral hips, course of disease, staging, cause, and region were also analyzed. RESULTS: Seventy patients were of complicated constitutions, while 60 patients were of single constitution. Among the 60 single constitution cases, yang-deficiency constitution [18 (13.9%)], damp-heat constitution [10 (7.7%)], blood-stasis constitution [7 (5.4%)], and qi-deficiency constitution [7 (5.4%)] were mainly distributed. Of the complicated constitutions, yang-deficiency dominated constitution occupied the top ratio [30 (23.1%)], followed by blood-stasis dominated constitution [15 (11.5%)], damp-heat dominated constitution [9 (6.9%)]. By putting them together, yang-deficiency constitution occupied the top constitution of CM [48 (36.9%)], followed by blood-stasis constitution [ 22 (16.9%)] and damp-heat constitution [19 (14.6%)]. The aforesaid three constitutions accounted for 68.5% of the total. There were no statistical distribution differences in gender, age, single or bilateral hips, course of disease, staging, or cause. CONCLUSION: Yang-deficiency constitution, damp-heat constitution, and blood-stasis constitution were liable constitutions of CM in ONFH patients.

Necrosis avascular bilateral del escafoides (enfermedad de Preiser), una causa infrecuente de dolor de muñeca / Bilateral avascular necrosis of the scaphoid (Preiser’ Disease), a rare cause of wrist pain

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Effect of ibandronate on spontaneous osteonecrosis of the knee: a randomized, double-blind, placebo-controlled trial.

UNLABELLED: Based on this double-blind, placebo-controlled study, ibandronate has no beneficial effect on clinical and radiological outcome in patients with spontaneous osteonecrosis of the knee over and above anti-inflammatory medication. INTRODUCTION: Observational studies suggest beneficial effects of bisphosphonates in spontaneous osteonecrosis (ON) of the knee. We investigated whether ibandronate would improve clinical and radiological outcome in newly diagnosed ON. METHODS: In this randomized, double-blind, placebo-controlled trial, 30 patients (mean age, 57.3 ± 10.7 years) with ON of the knee were assigned to receive either ibandronate (cumulative dose, 13.5 mg) or placebo intravenously (divided into five doses 12 weeks). All subjects received additional treatment with oral diclofenac (70 mg) and supplementation with calcium carbonate (500 mg) and vitamin D (400 IU) to be taken daily for 12 weeks. Patients were followed for 48 weeks. The primary outcome was the change in pain score after 12 weeks. Secondary endpoints included changes in pain score, mobility, and radiological outcome (MRI) after 48 weeks. RESULTS: At baseline, both treatment groups (IBN, n = 14; placebo, n = 16) were comparable in relation to pain score and radiological grading (bone marrow edema, ON). After 12 weeks, mean pain score was reduced in both ibandronate- (mean change, -2.98; 95% CI, -4.34 to -1.62) and placebo- (-3.59; 95% CI, -5.07 to -2.12) treated subjects (between-group comparison adjusted for age, sex, and osteonecrosis type, p = ns). Except for significant decrease in bone resorption marker (CTX) in ibandronate-treated subjects (p < 0.01), adjusted mean changes in all functional and radiological outcome measures were comparable between treatment groups after 24 and 48 weeks. CONCLUSIONS: In patients with spontaneous osteonecrosis of the knee, bisphosphonate treatment (i.e., IV ibandronate) has no beneficial effect over and above anti-inflammatory medication.

Exogenous phytoestrogenic molecule icaritin incorporated into a porous scaffold for enhancing bone defect repair.

This study was designed to develop a bioactive scaffold to enhance bone defect repair in steroid-associated osteonecrosis (SAON). Icaritin, a metabolite of the herb Epimedium, has been identified as an angiogenic and osteogenic phytomolecule. Icaritin was homogenized into poly lactic-co-glycolic acid/tricalcium phosphate (PLGA/TCP) to form an icaritin-releasing porous composite scaffold (PLGA/TCP/icaritin) by fine-spinning technology. In vitro, high performance liquid chromatography was used to determine the release of icaritin during degradation of PLGA/TCP/icaritin. The osteogenic effects of PLGA/TCP/icaritin were evaluated using rat bone marrow mesenchymal stem cells (BMSCs). In vivo, the osteogenic effect of PLGA/TCP/icaritin was determined within a bone tunnel after core decompression in SAON rabbits and angiography within scaffolds was examined in rabbit muscle pouch model. In vitro study confirmed the sustainable release of icaritin from PLGA/TCP/icaritin with the bioactive scaffold promoting the proliferation and osteoblastic differentiation of rat BMSCs. In vivo study showed that PLGA/TCP/icaritin significantly promoted new bone formation within the bone defect after core decompression in SAON rabbits and enhanced neovascularization in the rabbit muscle pouch experiment. In conclusion, PLGA/TCP/icaritin is an innovative local delivery system that demonstrates sustainable release of osteogenic phytomolecule icaritin enhancing bone repair in an SAON rabbit model. The supplement of scaffold materials with bioactive phytomolecule(s) might improve treatment efficiency in challenging orthopedic conditions.

Osteonecrosis de los maxilares asociada al uso de bifosfonatos / Biphosphonate-related osteonecrosis of the jaws

Los bifosfonatos son drogas utilizadas en el tratamiento de tumores óseos metástasis óseas, y en otras afeccionesóseas como el mieloma múltiple. Se utilizan también para la prevención y tratamiento de la osteoporosis enmujeres posmenopáusicas. El número de pacientes en tratamiento con estas drogas es cada vez mayor y demanera concomitante hay un número creciente de informes sobre la osteonecrosis de mandíbula asociada a su uso. Las lesiones maxilares presentan gran variabilidad clínica. El cuadro se ha relacionado con: tipo de bifosfonatos, tiempo de tratamiento, dosis de tratamiento, vía de administración y antecedente de tratamiento odontológico, generalmente exodoncia. El objetivo de este trabajo es proveer información sobre las lesiones óseas maxilares (osteonecrosis) que aparecen en pacientes que utilizan bifosfonatos y las medidas terapéuticas yprofilácticas a ser empleadas ante la aparición de las mismas para lo cual se realizó una revisión de la literaturacientífica disponible a la fecha. El propósito es alertar a los profesionales y futuros profesionales sobre estapatología, haciendo énfasis también en la importancia de la comunicación entre los médicos generales que prescribenbifosfonatos y los odontólogos, quienes deben estar preparados para enfrentar el desafío de su diagnóstico, tratamiento y sobre todo la prevención de su aparición. (AU)

Osteonecrosis de los maxilares asociada al uso de bifosfonatos / Biphosphonate-related osteonecrosis of the jaws

Los bifosfonatos son drogas utilizadas en el tratamiento de tumores óseos metástasis óseas, y en otras afeccionesóseas como el mieloma múltiple. Se utilizan también para la prevención y tratamiento de la osteoporosis enmujeres posmenopáusicas. El número de pacientes en tratamiento con estas drogas es cada vez mayor y demanera concomitante hay un número creciente de informes sobre la osteonecrosis de mandíbula asociada a su uso. Las lesiones maxilares presentan gran variabilidad clínica. El cuadro se ha relacionado con: tipo de bifosfonatos, tiempo de tratamiento, dosis de tratamiento, vía de administración y antecedente de tratamiento odontológico, generalmente exodoncia. El objetivo de este trabajo es proveer información sobre las lesiones óseas maxilares (osteonecrosis) que aparecen en pacientes que utilizan bifosfonatos y las medidas terapéuticas yprofilácticas a ser empleadas ante la aparición de las mismas para lo cual se realizó una revisión de la literaturacientífica disponible a la fecha. El propósito es alertar a los profesionales y futuros profesionales sobre estapatología, haciendo énfasis también en la importancia de la comunicación entre los médicos generales que prescribenbifosfonatos y los odontólogos, quienes deben estar preparados para enfrentar el desafío de su diagnóstico, tratamiento y sobre todo la prevención de su aparición.

Pamidronate treatment of steroid associated osteonecrosis in young patients treated for acute lymphoblastic leukaemia--two-year outcomes.

AIMS: To assess outcomes of young patients with osteonecrosis (ON) treated with pamidronate in terms of relief of pain, prevention of progress and bony collapse of involved area. PATIENTS AND METHODS: A non-randomised interventional study in six patients with a history of acute lymphoblastic leukaemia (ALL) for which treatment protocols included long-term, high dose use of glucocorticoids. Subsequent development of ON was treated with a bisphosphonate (pamidronate) for 2 years. Mobility and pain control were assessed regularly with MRI and X-ray of affected areas at 0, 12 and 24 months. RESULTS: Reduction in pain was reported in four of six patients in the first year with increased mobility. Two patients who had radiological evidence of joint destruction prior to treatment and when continued on corticosteroids reported no improvement in pain or mobility. In the second year, patients who started treatment in the first few months after diagnosis were stable while patients who had treatment initiated later deteriorated but had less pain than prior to treatment with pamidronate. MRIs of affected areas were completely unchanged over 2 years. X-rays revealed no new bony collapse in four of six patients after 12 months of treatment. However, three of six patients continued to undergo extensive collapse of femoral heads (one at 12 months, two at 24 months) and all these required urgent hip replacement. CONCLUSION: Pamidronate treatment has a palliative effect in control of pain and may delay the natural history of bony collapse in the acute phase of ON, especially in early treated patients, but does not prevent late bone collapse and joint destruction in corticosteroid treated patients with ALL. Larger studies are needed to provide evidence as to whether bisphosphonate is indicated for treatment of ON for patients using corticosteroids.

Osteonecrosis como causante de fracado de artroplastia total de rodilla / Osteonecrosis as the cause of failure of total knee arthroplasty

Exponemos el caso de una paciente en la que coexistían dos procesos articulares: artritis reumatoide y una intensa osteoporosis. Padecía deformidad en valgo de rodilla derecha con dolor incapacitante por afectación inflamatoria reumatoidea. Se procedió a su tratamiento mediante artroplastia total de rodilla, la cual fracasó por osteonecrosis en cóndilo femoral medial e intensa osteoporosis. La corticoterapia administrada como tratamiento de su patología inflamatoria resultó el factor determinante en este fracaso. Se recurrió a cirugía de rescate puesto que, una vez aparecida la osteonecrosis, el único tratamiento que procede actualmente es tratar sus secuelas y reducir sus factores favorecedores. Terapias con alendronato, vitamina D y suplementos de calcio están demostrando su eficacia en la prevención de osteonecrosis tras artroplastia, instaurándose ya su uso profiláctico en algunos centros con óptimos resultados

We expose the case of a patient in which two joint proceses coexisted reheumatoid artritis and an intense osteoporosis. She suffered deformity in valgus of right knee with incapacitating pain for rheumatic inflammatory affectation. We proceeded to their treatment by means of total knee arthroplasty, which failed for the presence of osteonecrosis in medial femoral condile and intense osteoporosis. The esteroids administered treatment of its inflammatory pathology were the decisive factor in this failure. We practised rescue surgery since, once appeared the osteonecrosis, the only treatment that proceeds at the moment is to treat its sequels and to reduce its favouring factors. Therapies with alendronate, vitamin D and supplements of calcium are demonstrating their effectiveness in the osteonecrosis prevention after artroplastia, being already established their use for profilaxis in some centers with good results

Orofacial neurogenic pain and maxillofacial ischemic osteonecrosis. A review.

Cavitary alveolar osteopathy was described as an oral disorder of infectious origin characterized by the presence of osteopathic alveolar cavity lesions of significant size though radiologically undetectable and secondary to dental extractions for chronic infectious processes of the alveolar bone of the jaws. Such cavitary alveolar osteopathy has been implicated as a common cause in the origin of idiopathic trigeminal neuralgia and atypical facial pain. The concept of cavitary alveolar osteopathy caused by ischemic necrosis of alveolar bone was introduced in 1992. Recent coagulation studies have reported ischemic alterations in alveolar bone marrow as a cause of cavitation; following tooth extraction, maxillary osteonecrosis could result from thrombosis with or without hyperfibrinolysis, which in turn would lead to obstruction of the vascular spaces -- thereby compromising regional blood flow.

Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft.

OBJECTIVE: To discuss the case of a 79-year-old man who had a delayed posttraumatic vertebral collapse and an intravertebral vacuum cleft. The patient had been on long-term corticosteroid therapy. A discussion of Kummell's disease and the controversy surrounding the etiology of the condition is also presented. CLINICAL FEATURES: Six weeks before coming to the clinic, the patient remembered twisting, hearing a pop, and having severe low back pain. Two weeks after the incident, while hospitalized for bacterial cellulitis, he underwent lumbar spine radiography. The radiographs showed degenerative changes and remote (healed) compression fractures but did not demonstrate any deformity of L2. Four weeks later, he sought care for persistent low back pain. Radiographs revealed marked compression of the L2 vertebral body with an intravertebral vacuum phenomenon. INTERVENTION AND OUTCOME: The patient was referred to his geriatrician for evaluation as a candidate for vertebroplasty or other stabilization procedures. He required a moderately high dose (60 mg) of prednisone daily to combat the symptoms of myasthenia gravis; therefore, the prognosis appears unfavorable for this patient. CONCLUSION: Clinical research is needed to determine the definitive etiology and pathophysiology of Kummell's disease. This case demonstrates that the intravertebral vacuum is a dynamic entity, subject to changes in size and shape. Previous case reports have suggested that Kummell's disease only presents as a linear, horizontal cleft. This disease needs further investigation to determine the true correlation between radiographic signs and the underlying pathophysiology.