Chronic Recurrent Multifocal Osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an underrecognized autoinflammatory disease affecting the skeletal system. Its vague symptoms are often first attributed to growing pains, infection, or malignancy, which can lead to a delay in diagnosis for days to years. Untreated CRMO has the potential to cause debilitating skeletal deformities, arthritis, and chronic pain; hence early recognition and treatment are paramount. MRI is the gold standard for diagnosis. Treatment consists of various antiinflammatory medications and may also include bisphosphonates if vulnerable skeletal sites are involved. Even when treated, the disease may have a relapsing course lasting years.

Treatment of Medication-Related Osteonecrosis of the Jaw: Controversies in Causality and Therapy.

Medication-related osteonecrosis of the jaw (MRONJ) is a most interesting, complex and "elusive" condition seen by the oral health care provider. It is plagued by controversy and although a wealth of research has created clinical treatment databases, there is no "gold standard" algorithm to be applied in a universal fashion. The purpose of this article is to explore several controversies associated with the etiology(s), staging, treatments, and long-term resolution of MRONJ in patients who are treated by the oral health care provider. Controversies for optimizing prevention, and disease control will also be discussed from an interdisciplinary perspective.

Medication adherence of bisphosphonate weekly or monthly regimens in patients with osteoporosis using a nationwide large claims database.

Bisphosphonate (BPN) therapy, which mainly targets osteoporosis, evolves rapidly, leaving patients and physicians with a substantial collection of BPN regimen options. In this study, we aimed to clarify BPN medication adherence between weekly and monthly regimens using a nationwide claims database in Japan. We analyzed 5,016 patients with a screening period of 3 months and a 12 month observation period who started using BPN. We used propensity score matching with baseline patient background after dividing the patients into two groups: weekly and monthly BPN users. Medication adherence was calculated using proportion days cover (PDC). A PDC of > 80% was 55.9% and 52.5% in monthly and weekly formulas, respectively, during the 12 months after initiating BPN treatment. PDC-based BPN medication adherence was higher in monthly regimens than in weekly regimens (66.3±34.0 vs. 64.1±36.8%). No differences were found in the proportion of patients with > 80% medication adherence between the monthly and weekly regimens after stratifying patient background using propensity score matching. Our clinical findings highlight the importance of closely monitoring BPN medication adherence, particularly during the initial year of therapy. Notably, half of the patients with osteoporosis exhibited low medication adherence. Therefore, prioritizing monthly regimens over weekly regimens is crucial to promote BPN adherence and ensure optimal treatment outcomes.

Dynamic blood flow imaging with 99mTc-hydroxymethylene diphosphonate as a therapeutic response marker in patients with Raynaud's phenomenon.

We evaluated the predictive value of dynamic blood flow scintigraphy with 99mTc-HDP (hydroxymethylene diphosphonate) for therapeutic response in patients with Raynaud's phenomenon (RP). Eighty patients who underwent dynamic blood flow scintigraphy using the one-hand chilling method were enrolled. We analyzed the quantitative variables as the ratio of chilled fingers to ambient fingers (CAfinger), that of the chilled hand to ambient hand (CAhand), and that of chilled fingers to ambient palm (FPR) (CAFPR) at 15 and 30 s after 99mTc-HDP bolus injection. Total cumulative radioactivity counts for 180 s were obtained. We evaluated the clinical utility of these quantitative parameters with other clinical variables, including RP severity, therapeutic compliance, types of RP, and scintigraphic interpretation of findings in patients with RP. Fifty-two patients showed poor therapeutic response. There were significant differences between good- and poor-therapeutic responder groups in RP intensity (p = 0.003), CAfinger15s (p = 0.008), CAfinger30s (p = 0.002), CAfinger180s (p = 0.011), CAhand15s (p = 0.008), CAhand30s (p = 0.007), CAhand180s (p = 0.017), CAFPR30s (p = 0.004), and CAFPR180s (p = 0.002). After multivariate logistic regression analysis, only CAfinger30s (p = 0.002) had an independent predictive value of the therapeutic response. 99mTc-HDP dynamic blood flow scintigraphy could be helpful in predicting the therapeutic response in patients with RP.

Comprehensive Clinical Literature Review of Managing Bone Metastases in Breast Cancer: Focus on Pain and Skeletal-Related Events.

BACKGROUND: Bone metastases are the most common site of metastatic disease in breast cancer and can result in significant pain and an increased risk of skeletal-related events (SREs). Uncontrolled pain can further lead to negative outcomes. OBJECTIVES: The aim is to provide oncology nurses with the latest evidence on the management of bone metastases in metastatic breast cancer (MBC) with a focus on pain and SREs. METHODS: A literature search was conducted using the Embase®, PubMed®/MEDLINE®, CINAHL®, and Cochrane Library databases. Clinical trials, retrospective studies, systematic reviews, meta-analyses, and practice guidelines, as well as one high-level conference abstract, were reviewed. FINDINGS: Options for managing bone metastases in MBC include surgical and interventional strategies, radiation, and bone-modifying agents. Management plans frequently include a combination of these modalities. More information is needed to better define the role of bone-directed therapies in MBC, particularly as they relate to nursing care.

Pre-existing medication-related osteonecrosis of the jaw before dental extraction.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse event, most commonly associated with dental extractions as a predisposing event. However, it is possible that established MRONJ may be existent before dental extractions and is mistaken for odontogenic disease. The provision of a dental extraction will lead to clinically obvious MRONJ with the cause being attributed to tooth removal. We present a case series of ten patients with pre-existing necrosis of the jaw before dental extraction.Retrospective data were collected on ten patients who presented to the oral surgery department between 2017-2021, diagnosed with pre-existing necrosis. A diagnosis of pre-existing MRONJ was made based on the identification of necrotic bone clinically, either with plain film or cone beam computed tomography (CBCT). Patients with pre-existing necrosis presented with a range of symptoms, including pain, swelling and tooth mobility. Plain film imaging revealed a variety of findings, including periapical radiolucency, periodontal ligament widening and bone loss. CBCT imaging confirmed a necrotic pattern of bone destruction confirming a diagnosis of pre-existing MRONJ.There is increasing evidence to suggest that local inflammation can be a predisposing factor for MRONJ development as opposed to surgical intervention. This case series provides early insight into the presentation of pre-existing MRONJ.

Long-term consequences of osteoporosis therapy with bisphosphonates.

Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.

Obesity influences the development of bisphosphonate-induced osteonecrosis in Wistar rats.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by bone exposure for more than eight weeks in patients who have used or been treated with antiresorptive or antiangiogenic drugs, without a history of radiation therapy or metastatic diseases in the jaws. Obesity is associated with changes in periodontal tissues and oral microbiota that are linked to bone alterations. This study aimed to analyze the influence of obesity on the development of bisphosphonate-induced osteonecrosis. The experiment randomly and simply divided 24 male Wistar rats (Rattus norvegicus) into four groups: healthy, with osteonecrosis, obese, and obese with osteonecrosis (n=6 per group). Osteonecrosis was induced through weekly intraperitoneal injection for eight weeks at a dose of 250 µg/kg of zoledronic acid in a 4 mg/5 mL solution, combined with trauma (exodontia). Obesity was induced through a high glycaemic index diet. Each group was qualitatively and quantitatively evaluated regarding the development of models and pathological anatomy of the lesions. The results were expressed in mean percentage and standard deviation and statistically analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test, with a significance level of 5% (p<0.05) to establish differences found between the groups. Animals in the osteonecrosis group and the obese with osteonecrosis group presented larger necrosis areas (averages: 172.83±18,19 µm2 and 290.33±15,77 µm2, respectively) (p<0,0001). Bone sequestration, hepatic steatosis, and increased adipocyte size were observed in the obese group (average: 97.75±1.91 µm2) and in the obese with osteonecrosis group (average: 98.41±1.56 µm2), indicating greater tissue damage in these groups (p<0,0001). All parameters analyzed (through histological, morphometric, and murinometric analyses) increased for the obese and obese with osteonecrosis groups, suggesting a possible influence of obesity on the results. However, further studies are needed to confirm the role of obesity in the possible exacerbation of osteonecrosis and understand the underlying mechanisms.

Three-dimensional clinical assessment for MRONJ risk in oncologic patients following tooth extractions.

OBJECTIVES: To identify clinical and local radiographic predictors for medication-related osteonecrosis of the jaws (MRONJ) by the assessment of pre-operative CBCT images of oncologic patients treated with anti-resorptive drugs (ARDs) undergoing tooth extractions. METHODS: This retrospective, longitudinal, case-control study included clinical and imaging data of 97 patients, divided into study and control group. Patients in the study group (n = 47; 87 tooth extractions) had received at least one dose of ARD, undergone tooth extraction(s), and had a pre-operative CBCT. An age-, gender-, and tooth extraction-matched control group (n = 50; 106 tooth extractions) was selected. Three calibrated, blinded, and independent examiners evaluated each tooth extraction site. Statistical analysis used χ2/Fisher's exact/Mann-Whitney U test to contrast control and study group, ARD type used, and sites with or without MRONJ development. p-value ≤ 0.05 was considered significant. RESULTS: From the study group, 15 patients (32%) and 33 sites (38%) developed MRONJ after tooth extraction. When controls were compared to study sites, the latter showed significantly more thickening of the lamina dura, widened periodontal ligament space, osteosclerosis, osteolysis, and sequestrum formation. In the study group, MRONJ risk significantly increased in patients who had multiple tooth extractions, were smokers, and had shorter drug holidays. Periosteal reaction and sequestrum formation may indicate latent MRONJ lesions. Additionally, patients given bisphosphonates showed considerably more osteosclerosis than those given denosumab. CONCLUSIONS: Periosteal reaction and sequestrum formation are suspected to be pre-clinical MRONJ lesions. Furthermore, ARD induced bony changes and radiographic variations between ARD types were seen.

Effects of bisphosphonates and treadmill exercise on bone and kidney in adenine-induced chronic kidney disease rats.

INTRODUCTION: The increasing prevalence of osteoporosis and chronic kidney disease (CKD) due to the aging of society has highlighted the need for development of effective treatments for elderly patients. This study examined whether the combination of treadmill exercise therapy and alendronate (ALN) can improve bone mineral density (BMD) and bone strength without worsening renal function in adenine-induced CKD model rats. MATERIALS AND METHODS: 8-week-old male Wistar rats (n = 70) were divided into experimental groups based on the treatment protocol, i.e., non-CKD (control), vehicle only (CKD), ALN only, exercise only, and combined ALN plus exercise. A 0.75% adenine diet was used to induce CKD. Groups were killed at either 20 or 30 weeks of age. Comprehensive assessments included serum and urine biochemistry tests, renal histology, bone histomorphometry, BMD measurement, micro-computed tomography examinations, and biomechanical testing. RESULTS: Blood biochemistry tests, urine analyses and histological evaluations of the kidney demonstrated that ALN treatment did not worsen renal function or kidney fibrosis in moderate-stage CKD model rats. Both ALN and treadmill exercise significantly suppressed bone resorption (p < 0.05-p < 0.01). Moreover, ALN monotherapy and combined ALN and treadmill exercise significantly improved BMD of the lumbar spine and femur, bone microstructure, and trabecular bone strength (p < 0.05-p < 0.01). Treadmill exercise was also shown to decrease cortical porosity at the mid-diaphysis of the femur and improve kidney fibrosis. CONCLUSION: The combination of ALN and treadmill exercise is effective in improving BMD, the microstructure of trabecular and cortical bone, and bone strength, without compromising renal function in adenine-induced CKD model rats.

Reliability of early stage symptoms/clinical findings of osteonecrosis of the jaw: Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected stage 0 ONJ between patients treated with sequential therapy comprising weekly teriparatide for 72 weeks followed by alendronate for 48 weeks vs. those who received monotherapy with alendronate for 120 weeks. MATERIALS AND METHODS: Suspected stage 0/1 ONJ was defined by non-specific symptoms. Tooth mobility and periodontal symptoms (gingival bleeding, swelling, and/or pain) were selected as clinical findings of suspected stage 0 ONJ. Poisson regression models were applied to calculate the incidence rate ratios of suspected stage 0/1 between the teriparatide group (TG) and alendronate group (AG). Generalized linear models were used to calculate the risk ratios of clinical findings between groups. RESULTS: Two hundred and sixty-one participants in the TG and 344 in the AG answered a structured questionnaire on oral health and were included in this study. There were no significant differences between the groups in the incidence rate of suspected stage 0/1 ONJ at both 72 and 120 weeks. The risk ratio of the TG to AG for tooth mobility was 0.34 (95% confidence interval [CI] 0.13-0.88, p = 0.02) at 72 weeks and 0.90 (95% CI 0.40-2.03, p = 0.83) at 120 weeks. The incidence rate of tooth mobility related to periodontal symptoms decreased in the TG and increased in the AG during the study. CONCLUSION: Tooth mobility accompanied by clinical periodontal symptoms may be a useful early sign of stage 0 ONJ.

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.

Bone Health in the Transgender Population.

¼ Transgender women are more susceptible to low bone mineral density (BMD) before initiating gender-affirming hormone therapy (GAHT), and while bone density initially improves with GAHT, it gradually declines while still remaining above baseline. Transgender women older than 50 years have a comparable fracture risk as age-matched cisgender women. Transgender men typically have normal or increased BMD before initiating and while receiving GAHT and are not at increased risk of fractures.¼ Transgender youth who receive puberty-blocking medications experience either no change or a slight decrease in BMD that returns to baseline after initiating GAHT.¼ It is important to abide by the International Society for Clinical Densitometry guidelines whenever ordering, performing, or reading a BMD scan for a gender-diverse patient.¼ There are no specific guidelines concerning vitamin D and calcium supplementation or the use of bisphosphonates in the transgender population, so the current recommendation is to abide by the guidelines for cisgender individuals.

Denosumab administration for bone metastases from solid tumors: a retrospective cross-sectional study.

BACKGROUND: Little is known on how denosumab reduces skeletal-related events (SREs) by bone metastases from solid tumors. We sought to evaluate the effect of denosumab administration in patients with bone metastases from solid tumors. METHODS: Data of patients treated with denosumab were collected from electronic medical charts (n = 496). Eligible participants in this study were adult patients (age ≥ 18 years) with metastatic bone lesions from solid tumors treated with denosumab. SREs, surgical interventions, the spinal instability neoplastic score (SINS) for spinal region, and Mirels' score for the appendicular region were evaluated. To assess whether denosumab could prevent SREs and associated surgery, the SINS and Mirels' score were compared between patients with and without SREs. RESULTS: A total of 247 patients (median age, 65.5 years old; median follow-up period, 13 months) treated with denosumab for metastatic bone lesions from solid tumors were enrolled in this study. SREs occurred in 19 patients (7.7%). SREs occurred in 2 patients (0.8%) who took denosumab administration before SREs. Surgical interventions were undertaken in 14 patients (5.7%) (spinal and intradural lesions in five patients and appendicular lesions in nine patients). The mean SINS of patients without SREs compared to those with SREs were 7.5 points and 10.2 points, respectively. The mean Mirels' scores of non-SREs patients and those with SREs were 8.07 points and 10.7 points, respectively. Patients with SREs had significantly higher Mirels' score than non-SREs patients (p < 0.01). Patients with SREs had higher SINS than non-SREs patients (p = 0.09). CONCLUSIONS: SREs occurred in patients with higher SINS or Mirels' scores. Two patients suffered from SREs though they took denosumab administration before SREs. Appropriate management of denosumab for patients with bone metastasis is significant. Surgical interventions may be needed for patients who with higher SINS or Mirel's scores.

Osteonecrosis maxilar relacionada con la medicación: el papel del radiólogo / Medication-related osteonecrosis of the jaw: the radiologist's role

En las últimas décadas se ha descrito ampliamente y se ha llegado a conocer en profundidad un temido efecto adverso de los bisfosfonatos, la osteonecrosis maxilar, que consiste en la destrucción ósea de parte del hueso maxilar como consecuencia del consumo de estos fármacos antirresortivos. En los últimos años han salido a la luz nuevos fármacos que también pueden ocasionar osteonecrosis maxilar, como algunos anticuerpos monoclonales o fármacos antiangiogénicos. Es por esto por lo que el término de “osteonecrosis maxilar por bisfosfonatos” ha quedado obsoleto, prefiriéndose el término de “osteonecrosis maxilar relacionada con la medicación”. El objetivo de esta revisión es describir las características radiológicas de la osteonecrosis maxilar relacionada con la medicación que, aunque son inespecíficas, es importante que el radiólogo las reconozca en el marco clínico adecuado.(AU)

In recent decades, the dreaded adverse effect of bisphosphonates, osteonecrosis of the jaw, has been widely reported and described in detail. Osteonecrosis of the jaw consists of the destruction of part of the maxilla as a consequence of these antiresorptive drugs. In recent years, new drugs that can also cause osteonecrosis of the jaw (e.g., some monoclonal antibodies or antiangiogenic drugs) have come on the market. For this reason, the term “bisphosphonate-related osteonecrosis of the jaw” has been replaced with “medication-related osteonecrosis of the jaw (MRONJ). This review aims to describe the radiologic characteristics of MRONJ that, although nonspecific, radiologists need to recognize in the appropriate clinical context.(AU)