Denosumab-Induced Medication-Related Osteonecrosis of the Jaw (DRONJ): A 5-Year Retrospective Cohort Study

Denosumab (Dmab) has been suggested as a first-line therapy for osteoporotic patients. However, a standardized protocol for the prevention of Dmab induced medication-related osteonecrosis of the jaw (MRONJ) has not yet been established. Thus, we investigated the factors that can affect Dmab induced MRONJ (DRONJ) to elucidate the relationship between invasive dental treatment and Dmab administration in patients who underwent Dmab and invasive dental treatment (especially tooth extraction) between October 2016 and March 2020. Four of the 98 patients developed MRONJ before and after tooth extraction. Two out of 4 patients developed MRONJ regardless of invasive treatment after Dmab administration and proceeded with extraction, and one patient developed DRONJ after Dmab administration and extraction. The other patient underwent a tooth extraction without osteoporosis treatment, and spontaneous DRONJ developed after Dmab administration. All MRONJ/DRONJ cases reported in this study show that MRONJ/DRONJ can develop as chronic inflammation without invasive dental treatment, therefore, implementing preventive dental treatment before initiating Dmab treatment is necessary to reduce the likelihood of DRONJ.

m6A Methylation Regulates Osteoblastic Differentiation and Bone Remodeling

Osteoporosis is a prevalent bone disease of the aging population, which is characterized by a decrease in bone mass because of the imbalance of bone metabolism. Although the prevention and treatment of osteoporosis have been explored by different researchers, the mechanisms underlying osteoporosis are not clear exactly. N6 methyladenosine (m6A) is a methylated adenosine nucleotide, which functions through its interaction with the proteins called “writers,” “readers” and “erasers.” The epigenetic regulation of m6A has been demonstrated to affect mRNA processing, nuclear export, translation, and splicing. At the cellular level, m6A modification has been known to affect cell proliferation, differentiation, and apoptosis of bone-related cells, such as bone marrow mesenchymal stem cells (BMSC), osteoblasts, and osteoclasts by regulating the expression of ALP, Runx2, Osterix, VEGF, and other related genes. Furthermore, PTH/Pth1r, PI3K‐Akt, Wnt/β‐Catenin, and other signaling pathways, which play important roles in the regulation of bone homeostasis, are also regulated by m6A. Thus, m6A modification may provide a new approach for osteoporosis treatment. The key roles of m6A modification in the regulation of bone health and osteoporosis are reviewed here in this article.

When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis

Glucocorticoid-induced osteoporosis (GIOP) leads to fractures in up to 40% of patients with chronic glucocorticoid (GC) therapy when left untreated. GCs rapidly increase fracture risk, and thus many patients with anticipated chronic GC exposures should start anti-osteoporosis pharmacotherapy to prevent fractures. In addition to low awareness of the need for anti-osteoporosis therapy among clinicians treating patients with GCs, a major barrier to prevention of fractures from GIOP is a lack of clear guideline recommendations on when to start and stop anti-osteoporosis treatment in patients with GC use. The aim of this narrative review is to summarize current evidence and provide considerations for the duration of anti-osteoporosis treatment in patients taking GCs based on pre-clinical, clinical, epidemiologic, and pharmacologic evidence. We review the pathophysiology of GIOP, outline current guideline recommendations on initiating and stopping anti-osteoporosis therapy for GIOP, and present considerations for the duration of anti-osteoporosis treatment based on existing evidence. In each section, we illustrate major points through a patient case example. Finally, we conclude with proposed areas for future research and emerging areas of interest related to GIOP clinical management.

DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis

As one of the leading causes of bone fracture in postmenopausal women and in older men, osteoporosis worldwide is attracting more attention in recent decades. Osteoporosis is a common disease mainly resulting from an imbalance of bone formation and bone resorption. Pharmaceutically active compounds that both activate osteogenesis, while repressing osteoclastogenesis hold the potential of being therapeutic medications for osteoporosis treatment. In the present study, sesamin, a bioactive ingredient derived from the seed of Sesamum Indicum, was screened out from a bioactive compound library and shown to exhibit dual-regulating functions on these two processes. Sesamin was demonstrated to promote osteogenesis by upregulating Wnt/β-catenin, while repressing osteoclastogenesis via downregulating NF-κB signaling . Furthermore, DANCR was found to be the key regulator in sesamin-mediated bone formation and resorption . In an ovariectomy (OVX)-induced osteoporotic mouse model, sesamin could rescue OVX-induced bone loss and impairment. The increased serum level of DANCR caused by OVX was also downregulated upon sesamin treatment. In conclusion, our results demonstrate that sesamin plays a dual-functional role in both osteogenesis activation and osteoclastogenesis de-activation in a DANCR-dependent manner, suggesting that it may be a possible medication candidate for osteoporotic patients with elevated DNACR expression levels.

The osteoporosis treatment by gene therapy: a current approach and challenges

Osteoporosis is a worldwide disease characterized by reduction of bone mass and alteration of bone architecture resulting in increased bone fragility and increased fracture risk. Although it is seen in all age groups, gender, and races, it is more common in Caucasians (white race), older people, and women. With an aging population and longer life span, osteoporosis is increasingly becoming a global epidemic. Currently, it has been estimated that more than 200 million people are suffering from osteoporosis. Moreover, osteoporosis results in a decreased quality of life, increased disability-adjusted life span, and big financial burden to health insurance systems of countries that are responsible for the care of such patients. Therefore, increasing awareness in medical field, which, in turn, facilitates increase awareness of the normal populace, will be effective in preventing this epidemic.

All-cause mortality risk in aged femoral intertrochanteric fracture patients

Introduction The 1-year mortality rate after femoral intertrochanteric fracture is higher than that of femoral neck fracture, which also belongs to hip fracture (Cui et al. in Arch Osteoporos 14(1):55, 2019). With the application of the concept of co-management model of orthopedics and geriatrics, the short-term and long-term mortality of all types of hip fractures has decreased (Van Heghe et al. in Calcif Tissue Int, 2021, https://doi.org/10.1007/s00223-021-00913-5). However, the mortality of Chinese femoral intertrochanteric fracture patients under this model has not been reported in the literatures. Aim This paper aims to study the risk factors of postoperative all-cause mortality in aged patients with femoral intertrochanteric fracture under the co-management model of orthopedics and geriatrics. Materials and methods This is a single-center prospective cohort study based on the real world, under the co-management of orthopedics and geriatrics, 363 patients aged ≥ 65 years with femoral intertrochanteric fracture were enrolled and followed up for 2–3 years; 52 patients were lost to follow up. Age, gender, body mass index (BMI), history of comorbidities, hip Bone Mineral Density (BMD), fracture history, 25(OH)D level, hemoglobin level, anti-osteoporosis treatment were risk factors to be tested. Kaplan–Meier survival curves and multivariate Cox proportional hazards models were constructed to analyze the impact of factors on all-cause mortality. Results (1) Most of the dead patients were older (the mean age was 83.4 years, compared with 79.8 years for surviving patients), with more complications and without anti-osteoporosis medication; gender, pre-fracture history, BMI, total hip BMD, hemoglobin, 25(OH)D had no difference between the dead and the living patients. (2) Elderly patients with Intertrochanteric fracture can benefit from the early treatment of Zoledronic Acid (within 3 days after the operation). Conclusion Under the co-management of orthopedics and geriatrics, to Chinese patients with Femoral Intertrochanteric fracture, Doctors should pay more attention to their age and chronic disease, and give anti-osteoporosis treatment if allowed.

Diabetes, Obesity, and Osteoporosis in an Ethnically Diverse Population of Women Receiving Osteoporosis Screening

Osteoporosis screening by bone density (BMD) testing is recommended for women aged 65-75 years. However, patients with diabetes, a risk factor for fracture, often have higher body mass index (BMI) which contributes to higher BMD. These factors may vary by race/ethnicity. The relationship of diabetes (≥2 diagnoses and treatment), obesity (BMI ≥30), and BMD-defined osteoporosis (femoral neck BMD T-score ≤ -2.5) was examined in a diverse primary care population of 44,313 non-Hispanic White, 6,103 Black, 7,777 Hispanic, and 12,634 Asian women aged 65-75 years who underwent BMD screening. Those with recent fracture, osteoporosis treatment, bone disorders, and metastatic cancer were excluded. Modified log-Poisson regression was used to examine the association of diabetes and BMD-osteoporosis. Among 70,827 women, 18% had diabetes. The prevalence of diabetes was 2-fold higher in Black, Hispanic and Asian women compared to White women. Overall, women with diabetes (versus no diabetes) were more likely to be obese and, except for Hispanic women, less likely to have BMD-osteoporosis. In unadjusted analyses, diabetes was associated with lower risk of BMD-defined osteoporosis in White, Black, and Asian women, but not Hispanic women. However, the association was attenuated or no longer evident after adjusting for BMI, suggesting that the lower burden of BMD-osteoporosis in women with diabetes is mediated in part by higher BMI. These findings support consideration of diabetes when assessing fracture risk in women undergoing osteoporosis screening. However, more studies in non-White populations with a high burden of diabetes are important since these relationships appear to differ by race/ethnicity.