Cause Of Osteoporosis Research Articles

Management of Adrenal Cortical Adenomas: Assessment of Bone Status in Patients with (Non-Functioning) Adrenal Incidentalomas

Our aim is to analyse the bone profile in adults with (non-functioning) adrenal incidentalomas (AIs), specifically addressing the impact of autonomous cortisol secretion (ACS). This narrative review, based on a PubMed search from inception to February 2023 (case reports, non-ACS, and other secondary causes of osteoporosis were excluded), included 40 original studies, a total of 3046 patients with female prevalence (female:male ratio of 1921:1125), aged between 20.5 and 95.5 years old. This three decade-based analysis showed that 37 studies provided dual-energy X-ray absorptiometry (DXA) information; another five studies reports results on bone micro-architecture, including trabecular bone score (TBS), spinal deformity index, and high-resolution peripheral quantitative computed tomography; 20 cohorts included data on bone turnover markers (BTMs), while four longitudinal studies followed subjects between 1 and 10.5 years old (surgical versus non-adrenalectomy arms). Post-dexamethasone suppression test (DST) cortisol was inversely associated with bone mineral density (BMD). TBS predicted incidental vertebral fractures (VFx) regardless of BMD, being associated with post-DST cortisol independently of age and BMD. Low BTMs were identified in ACS, but not all studies agreed. An increased prevalence of ACS-related osteoporosis was confirmed in most studies (highest prevalence of 87.5%), as well as of VFx, including in pre-menopause (42.5%), post-menopause (78.6%), and male patients (72.7%) depending on the study, with a 10-fold increased incidental VFx risk up to a 12-fold increased risk after a 2-year follow-up. No specific medication against osteoporosis is indicated in ACS, but adrenalectomy (according to four studies) should be part of the long-term strategy. This bone profile case sample-based study (to our knowledge, one of the largest of its kind) showed that AIs, including the subgroup designated as having ACS, embraces a large panel of osseous complications. The level of evidence remains far from generous; there are still no homogenous results defining ACS and identifying skeletal involvement, which might be a consequence of different investigation clusters underling adrenal and bone assessments over time. However, bone status evaluations and associated therapy decisions remain an essential element of the management of adults with AIs-ACS.

Association Between Hip Bone Mineral Density and Mortality Risk After Hip Fracture: A Prospective Cohort Study.

Factors related to mortality after osteoporotic hip fracture (HF) have been investigated intensively, except for proximal femoral bone mineral density (BMD), which is also the primary cause of osteoporosis. In this study, we aimed to investigate the association of hip BMD with mortality risk after HF. Four hundred and eleven elderly patients with HF in Beijing, China, were included and prospectively followed up with a median time of 3years. At baseline, quantitative CT technique (QCT) was used to measure areal BMD (aBMD) of the unaffected hip. Areal BMDs of the total hip (TH), femoral neck (FN), trochanter (TR), and intertrochanter were analyzed with postoperative mortality as the primary outcome. A total of 394 patients (78.59 ± 7.59years, 75.4% female) were included in our final analysis, with 86 (82.23 ± 7.00years, 81.4% female) dead. All hip bone densities demonstrated a significant association with mortality risks in the unadjusted model, but only TR aBMD remained significantly correlated after adjusting for all covariates. Compared to the lower TR aBMD group, the higher TR aBMD group yielded significantly lower death risks (HR 0.21 95% CI 0.05-0.9, P = 0.036). Higher survival probabilities were observed for higher TH and TR aBMD in survival analysis (P < 0.001). Hip BMD, especially TR BMD assessed by QCT, is an independent risk factor for postoperative mortality following HF. QCT may present a promising avenue for opportunistic analysis in immobilized patients, providing valuable information for early detection and personalized interventions to enhance patient outcomes.

Severe osteoporosis in a young man with bilateral Cushing’s syndrome: a case report

BackgroundThe diagnosis of Cushing’s syndrome is challenging; however, through the clinical picture and the search for secondary causes of osteoporosis, it was possible to reach the diagnosis of the case reported. There was an independent, symptomatic ACTH hypercortisolism manifested by typical phenotypic changes, severe secondary osteoporosis and arterial hypertension in a young patient.Case presentationA 20-year-old Brazilian man with low back pain for 8 months. Radiographs showed fragility fractures in the thoracolumbar spine, and bone densitometry showed osteoporosis, especially when evaluating the Z Score (− 5.6 in the lumbar spine). On physical examination, there were wide violaceous streaks on the upper limbs and abdomen, plethora and fat increase in the temporal facial region, hump, ecchymosis on limbs, hypotrophy of arms and thighs, central obesity and kyphoscoliosis. His blood pressure was 150 × 90 mmHg. Cortisol after 1 mg of dexamethasone (24.1 µg/dL) and after Liddle 1 (28 µg/dL) were not suppressed, despite normal cortisoluria. Tomography showed bilateral adrenal nodules with more severe characteristics. Unfortunately, through the catheterization of adrenal veins, it was not possible to differentiate the nodules due to the achievement of cortisol levels that exceeded the upper limit of the dilution method. Among the hypotheses for the differential diagnosis of bilateral adrenal hyperplasia are primary bilateral macronodular adrenal hyperplasia, McCune–Albright syndrome and isolated bilateral primary pigmented nodular hyperplasia or associated with Carney’s complex. In this case, primary pigmented nodular hyperplasia or carcinoma became important etiological hypotheses when comparing the epidemiology in a young man and the clinical-laboratory-imaging findings of the differential diagnoses. After 6 months of drug inhibition of steroidogenesis, blood pressure control and anti-osteoporotic therapy, the levels and deleterious metabolic effects of hypercortisolism, which could also impair adrenalectomy in the short and long term, were reduced. Left adrenalectomy was chosen, given the possibility of malignancy in a young patient and to avoid unnecessary definitive surgical adrenal insufficiency if the adrenalectomy was bilateral. Anatomopathology of the left gland revealed expansion of the zona fasciculate with multiple nonencapsulated nodules.ConclusionThe early identification of Cushing’s syndrome, with measures based on the assessment of risks and benefits, remains the best way to prevent its progression and reduce the morbidity of the condition. Despite the unavailability of genetic analysis for a precise etiological definition, it is possible to take efficient measures to avoid future damage.

The role of neridronate in the management of osteoporosis: A meta-analysis.

It is estimated that 1 in 3 women and 1 in 5 men over the age of 50 worldwide will experience an osteoporosis fracture during their lives. Neridronate is a third-generation bisphosphonate with established efficacy in metabolic bone disease. It can be used in the treatment of osteoporosis. We aimed to conduct a meta-analysis of the effect of neridronate on the treatment of osteoporosis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) for reports published until August 31, 2021, related to neridronate and osteoporosis. The modification of the bone mineral density (BMD, g/cm2) of the patient is the core indicator for neridronate treatment. Significant increases in the BMD of the lumbar spine (mean difference (MD) = 5.99, 95% confidence interval (95% CI): 3.96-8.02), femoral neck (MD = 4.51, 95% CI: 2.01-7.01) and total hip (MD = 2.55, 95% CI: 2.10-3.00) were found. Greater improvement in the BMD of the lumbar spine and femoral neck could also be detected in patients with postmenopausal osteoporosis than with other causes of osteoporosis. Moreover, significant decreases in serum C-telopeptide of collagen type I (sCTX, standardized mean difference (SMD) = -0.84, 95% CI: -1.32--0.37) and bone alkaline phosphatase (ALP, MD = -5.29, 95% CI: -7.31--3.26) levels were observed. The pool analysis of the selected clinical trials indicates the great benefit of neridronate in improving the condition of patients with osteoporosis of all causes, particularly patients with postmenopausal osteoporosis, which causes an increase in BMD as well as in sCTX and bone ALP levels.

Osteoporosis: Recent Advances

Osteoporosis is characterized by low bone mass, microarchitectural disruption, and skeletal fragility, resulting in decreased bone strength and an increased risk of fracture. Decreased bone strength is related to many factors in addition to bone mineral density (BMD), including rates of bone turnover, bone geometry, and microarchitecture.Osteoporosis has no clinical manifestations until there is a fracture. Complications of fractures include pain, deformity, disability, and loss of height. A clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture, particularly at the spine, hip, wrist, humerus, rib, and pelvis, without measurement of BMD.In the absence of a fragility fracture, BMD assessment by dual-energy x-ray absorptiometry (DXA) is the standard test to diagnose osteoporosis, according to the classification of the World Health Organization. A DXA T-score d”-2.5 is consistent with osteoporosis, whereas a T-score between -1 and -2.5 isosteopenia.All postmenopausal women with osteoporosis should have a history, physical examination, and basic laboratory evaluation. Initial laboratory studies should include a complete blood count (CBC), biochemistry profile, and 25- hydroxyvitamin D (25[OH]D).The need for additional laboratory evaluation depends upon the initial evaluation and Z-score. Women who have abnormalities on initial laboratory testing, suspicious findings on history and physical examination suggesting a secondary cause of osteoporosis, or Zscores d”-2 may require additional evaluation for these secondary causes.Lifestyle measures should be adopted universally to reduce bone loss in postmenopausal women. Lifestyle measures include adequate calcium and vitamin D, exercise, smoking cessation, counseling on fall prevention, and avoidance of heavy alcohol use. In general, 1200 mg of elemental calcium daily, total diet plus supplement, and 800 international units of vitamin D daily are advised. Many patients require vitamin D supplementation as it is difficult to achieve goals with diet alone. Postmenopausal women with established osteoporosis (T-score d”-2.5) or fragility fracture be treated with a pharmacologic agent. For the treatment of high-risk postmenopausal women with T-scores between -1.0 and -2.5, better to start pharmacologic therapy. Most women, for the initial treatmentoral bisphosphonates is good choice.For severe osteoporosis, some experts prefer initial treatment with an anabolic agent, whereas other experts prefer initial treatment with bisphosphonates. Teriparatide and abaloparatide are good anabolic agent. Romosozumab is an alternative. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 194

S-sulfhydration of SIRT3 combats BMSC senescence and ameliorates osteoporosis via stabilizing heterochromatic and mitochondrial homeostasis

Senescence of bone marrow mesenchymal stem cells (BMSCs) is one of the leading causes of osteoporosis. SIRT3, an essential NAD-dependent histone deacetylase, is highly correlated with BMSC senescence-mediated bone degradation and mitochondrial/heterochromatic disturbance. S-sulfhydration of cysteine residues favorably enhances SIRT3 activity by forming persulfides. Nevertheless, the underlying molecular mechanism of SIRT3 S-sulfhydration on mitochondrial/heterochromatic homeostasis involved in BMSC senescence remains unknown. Here, we demonstrated that CBS and CSE, endogenous hydrogen sulfide synthases, are downregulated with BMSC senescence. Exogenous H2S donor NaHS-mediated SIRT3 augmentation rescued the senescent phenotypes of BMSCs. Conversely, SIRT3 deletion accelerated oxidative stress-induced BMSC senescence through mitochondrial dysfunction and the detachment of the heterochromatic protein H3K9me3 from the nuclear envelope protein Lamin B1. H2S-mediated SIRT3 S-sulfhydration modification rescued the disorganized heterochromatin and fragmented mitochondria induced by the S-sulfhydration inhibitor dithiothreitol, thus leading to elevated osteogenic capacity and preventing BMSC senescence. The antisenescence effect of S-sulfhydration modification on BMSCs was abolished when the CXXC sites of the SIRT3 zinc finger motif were mutated. In vivo, aged mice-derived BMSCs pretreated with NaHS were orthotopically transplanted to the ovariectomy-induced osteoporotic mice, and we proved that SIRT3 ameliorates bone loss by inhibiting BMSC senescence. Overall, our study for the first time indicates a novel role of SIRT3 S-sulfhydration in stabilizing heterochromatin and mitochondrial homeostasis in counteracting BMSC senescence, providing a potential target for the treatment of degenerative bone diseases.

A case with late-onset Ornithine Transcarbamylase Deficiency as a possible cause of osteoporosis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

It hit two targets with one arrow. A case report of Cushing's syndrome as a contributing cause for osteoporosis and thrombosis in a 64-year-old female

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1403811: Rapidly Progressive Aortic Stenosis After Teriparatide Initiation: A Rare Case

Recombinant Parathyroid Hormone (rPTH) or Teriparatide is frequently used to manage severe osteoporosis due to its anabolic mode of action particularly in patients who are at a high risk of vertebral and non-vertebral fractures. Aortic valve stenosis is a common valve condition seen in the older population. There are multiple etiologies for aortic stenosis, but drug induced aortic stenosis is rare. Moreover, its natural history includes gradual progression towards severity. We present an interesting case of rapidly progressive aortic stenosis after teriparatide initiation. An 84-year-old female with history of hypertension, hyperlipidemia, atrial fibrillation presented to the endocrine clinic for management of osteoporosis. She was diagnosed with osteoporosis in 2000 at age 62. Initial etiology was assumed to be post-menopausal and was treated with oral bisphosphonates. As she had compression fractures of her spine while on treatment, secondary causes of osteoporosis were explored, and she was found to have primary hyperparathyroidism. Her labs were significant for PTH-84 pg/ml, Ca-10.8 mg/dl. She underwent parathyroidectomy in 2016 with normalization of PTH and calcium. After her surgery, she was treated with denosumab infusions every 6 months. She did well till June 2021. Her bone mineral density scores were stable throughout this period. At this point, she suffered bilateral atypical femoral fractures and was thought to be due to chronic anti-resorptive therapy. We stopped denosumab and transitioned her to teriparatide daily injections. She did well for 1 year but then presented to us for management in Aug 2022 prior to valve replacement for severe aortic stenosis. Her labs were significant for normal calcium, 25-hydroxy vitamin D and phosphorus levels. On reviewing her echocardiograms prior to and after initiation of teriparatide we found a rapid progression of her aortic stenosis from moderate to severe, based on mean gradients and peak velocities, over a span of 7 months. Natural progression of aortic stenosis from mild to severe happens over several years (mean duration-5 years), not just a few months. One possible explanation for this rapid progression seen in our patient is due to the presence of osteoblast like cells (arising from vascular endothelial cell precursor cells) in the aortic valve which appear to be stimulated by PTH and hence valve calcification/stenosis. On a thorough review of literature there were no clinical studies that have reported aortic stenosis progression from teriparatide use. To our knowledge, there was a single case report that reported the same phenomenon in Israel. As a result, we wanted to educate the community about the possible association between teriparatide use and worsening aortic stenosis in certain cases. Performing serial echocardiograms in high-risk patients and involving cardiology for early diagnosis and management is essential.

Evaluation of the effect of type II diabetes mellitus on Bone Mineral Density of Upper and Lower Limbs by Dual-Energy X-Ray Absorptiometry

Background: Bone mineral density has been assessed using Dual-Energy X-Ray Absorptiometry. Bone mineral density is measured according to the results of the Dual-Energy X-Ray Absorptiometry examination of the vertebral column and pelvis. Although diabetes mellitus type II (DM) is known to affect bone mineral density, at the present time this particular relationship is not clear. Objective: The aim of current study was to evaluate the effects of type II diabetes mellitus on bone mineral density of the upper and lower limbs as well as gender differences. Patients and Methods: This study involved 165 patients complaining of bone pain (85 males and 80 females), 85 patients of who suffered from diabetes, involving both genders. In addition, 90 apparently healthy volunteers had been studied and were considered to constitute the control group. All individuals (255) were studied regarding their bone mineral density via Dual-Energy X-Ray Absorptiometry for all parts of the body. Results: The Dual-Energy X-Ray Absorptiometry exam revealed highly statistically significant differences between the sides of the body in the same person. In addition, there were significant differences in bone mineral density between females and males, as well as between the control and patient groups with type II diabetes mellitus. Conclusion: Our results indicated that the bone mineral density of women was less than that in men in all cases (normal, osteoporosis, and diabetes mellitus type II (DM) with osteoporosis). Other results obtained from this research revealed that diabetes mellitus type II (DM) can be considered to be one of the major causes of osteoporosis in the general population

E061 Do proformas used in Fracture Liaison Service appointments reflect national osteoporosis clinical standards? A content analysis

Abstract Background/Aims Fracture Liaison Services (FLSs) identify people aged 50 and older who have had a fragility fracture to target for a bone health assessment, aiming to reduce future fractures. National osteoporosis guidelines outline key standards for service provision. Despite their common goal, the content of FLSs varies across the UK. FLSs, which are typically nurse-led, use proformas (documents used to plan, record and evaluate care using information collected within a clinical consultation) to guide them to meet these clinical standards. This study aimed to identify how much the FLS proformas reflect national osteoporosis guidelines and identify differences across services and gaps for improvement. Methods FLS clinicians taking part in the iFraP (Improving uptake of Fracture Prevention drug treatments) study usual care e-survey uploaded their service proformas for review. The content of the proformas were quantitatively analysed against the Royal Osteoporosis Society Clinical Standards for FLSs; the criteria assessed were: Standard 2 (investigations assessing risks of fragility fractures and falls, and possible secondary causes for osteoporosis are offered), Standard 3 (information and support is offered to people/carers) and Standard 4 (interventions are offered to reduce fragility fracture risks). Microsoft Excel was used to record if a criterion within the standards was met (present), partially met (mentioned) or not met (absent) in the proforma. Data was extracted by one reviewer, with a sample of proformas dual extracted to assess consistency. Discrepancies were resolved in discussions with a third reviewer. Elements of the proformas not considered in the standards was also extracted. Results A total of 8 proformas were analysed. All 8 proformas met (n = 7) or partially met (n = 1) standard 2 in investigating underlying secondary causes of a fracture, including assessing future fracture risk using FRAX or DXA; and assessing falls risk in over 65s. In standard 4, initiation of drug treatment and falls prevention referrals at the consultation was met in 7/8 proformas. Within Standard 3; giving information on osteoporosis and fracture risk was either partially met (n = 6) or not met (n = 2). Offering information related to lifestyle interventions was met in 4/8 proformas, and coping with pain and disability associated with a fracture was not assessed in any proformas. One proforma collected information on psychosocial factors related to loneliness and fuel poverty, not included in the standards. Conclusion This content analysis highlighted consistency across FLS proformas in identifying fractures, assessing fracture risk and initiating drug treatment. However, many FLS proformas indicated gaps in information offered to patients, especially in key areas related to pain and disability. Further research is needed to understand how quality of life can be assessed in the consultation to strengthen follow up support pathways (i.e. pain management) to enable patient centred-care for patients living with a fracture. Disclosure S. Abdelmagid: None. L. Bullock: None. Z. Paskins: None.

Surfactin suppresses osteoclastogenesis via the NF-κB signaling pathway, promotes osteogenic differentiation in vitro, and inhibits oestrogen deficiency-induced bone loss in vivo.

Fractures caused by osteoporosis (OP) are one of the main causes of death in the elderly, bringing a heavy burden to the country and society. The imbalance between osteoblast-mediated osteogenesis and osteoclast-mediated bone resorption is an important cause of OP. Therefore, finding drugs that can regulate this dynamic balance can be an important way to treat osteoporosis. Surfactin is a highly effective biosurfactant derived from Bacillus subtilis and it has been proven to have various pharmacological effects in previous studies, but its effect on bone metabolism remains unknown. Here, we performed a study on the role and mechanism of Surfactin in inhibiting osteoclastogenesis and its possible mechanism as well as the role in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). We investigated the effect of Surfactin on osteoclast differentiation and osteogenic differentiation in vitro and in vivo. The effect of Surfactin on the activity of osteoclastogenesis and osteogenesis was verified by CCK-8 assay, quantitative Real-time polymerase chain reaction (qPCR) and Western blotting analysis were used to verify the effect of Surfactin on osteoclast and osteogenic differentiation-specific genes and proteins. The effect of Surfactin on TRAP、ALP activity and mineral deposition was verified by TRAP、ALP and ARS staining. We then used an ovariectomy-induced osteoporosis mice model to observe the effect of Surfactin in vivo. Surfactin is noncytotoxic to BMMs, RAW264.7, and BMSCs. And it can effectively inhibit osteoclastogenesis and promote osteogenic differentiation. Moreover, we found that Surfactin can inhibit the differentiation of osteoclasts through the NF-κB signaling pathway. Surfactin can also alleviate bone loss in ovariectomy-induced osteoporosis mice. Our results suggest that Surfactin can inhibit osteoclastogenesis through the NF-κB signaling pathway, promote the osteogenic differentiation of BMSCs, and also can effectively alleviate bone loss in ovariectomy-induced osteoporosis mice.

Senescence of bone marrow fat cells: A new clue for glucocorticoid-induced bone deterioration

Glucocorticoid (GC)-induced osteoporosis is the most common secondary cause of osteoporosis, resulting in fractures and significant morbidity. In this issue of Cell Metabolism, Liu etal. reveal that in response to GCs, bone marrow adipocytes (BMAds) undergo rapid cellular senescence, triggering secondary senescence in bone marrow and causing bone deterioration.

Causes, Diagnose and Treatment of Osteoporosis

Osteoporosis is a chronic degenerative bone disease that seriously affects human health. This study analyzes the causes of osteoporosis in detail, expounds the common diagnostic methods, and proposes some corresponding treatment programs. Dual Energy X-ray Absorptiometry has high accuracy, image quality improvement, fast speed, rich clinical applications, and is suitable for scientific research. Quantitative Computed tomography measures true volumetric bone mineral density using initial CT data. This method is not affected by obesity, hyperosteoplasia, vascular calcification and vertebral size. Osteoporosis has the primary and secondary causes, primary osteoporosis covers the osteoporosis when women go through menopause (Type I), and osteoporosis of senile (Type II), and secondary osteoporosis refers to osteoporosis caused by certain medical conditions or medications. Exercise can help patients treat osteoporosis, and drugs could help prevent falls help prevent fractures. However, the treatment effect of most osteoporosis patients is not satisfactory. To treat osteoporosis, only one drug "single-handedly" has limited efficacy, and to effectively combat osteoporosis, it is necessary to emphasize "multi-service combat".

Isoliensinine suppresses bone loss by targeted inhibition of RANKL-RANK binding

BackgroundOsteoporosis, a systemic metabolic bone disease, is often caused by the disruption of dynamic equilibrium between osteoclasts and osteoblasts. Overactive bone resorption, in which osteoclasts play a major role, is one of the most common and major causes of osteoporosis. Less costly and more effective drug treatments for this disease are needed. Based on the combination of molecular docking techniques and in vitro cell assays, this study aimed to explore the mechanism by which Isoliensinine (ILS) protects the bone loss by inhibiting osteoclast differentiation. MethodsA virtual docking model based on molecular docking technology was used to investigate the interactions between ILS and the Receptor Activator of Nuclear Kappa-B (RANK)/Receptor Activator of Nuclear Kappa-B Ligand (RANKL).In this study, we determined the effective dose of action of ILS to inhibit osteoclast differentiation in vitro and, using bone resorption experiments, RT-CPR and Western Blot investigated the effects of ILS on bone resorption function and normal expression of osteoclast-associated genes and proteins, and validated potential mechanistic pathways. In vivo experiments revealed that ILS could inhibit bone loss through Micro-CT results.Finally, the molecular interaction between ILS and RANK/RANKL was investigated using biomolecular interaction experiments to verify the correctness and accuracy of the computational results. ResultsILS binds to RANK and RANKL proteins, respectively, through virtual molecular docking. The Surface Plasmon Resonance (SPR) experiment results revealed that phosphorylated JNK, ERK, P38, and P65 expression was significantly downregulated when ILS were targeted to inhibit RANKL/RANK binding. At the same time, the expression of IKB-a was significantly increased under the stimulation of ILS, which rescued the degradation of IKB-a. ILS can significantly inhibit the levels of Reactive Oxygen Species (ROS) and Ca2 + concentration in vitro. Finally, the results of Micro-CT showed that ILS can significantly inhibit bone loss in vivo, indicating that ILS has a potential role in the treatment of osteoporosis. ConclusionILS inhibits osteoclast differentiation and bone loss by preventing the normal binding of RANKL/RANK, affecting downstream signaling pathways, including MAPK.NF-KB, ROS, Ca2+, genes, and proteins.

Long non-coding RNA telomerase RNA elements improve glucocorticoid-induced osteoporosis by EZH2 to regulate DKK1.

Glucocorticoid-induced osteoporosis is the most common secondary cause of osteoporosis, which increases the risk of fracture. Long non-coding RNA telomerase RNA elements (TERC) has been proven to be closely related to osteoporosis. However, the role of TERC in glucocorticoid-induced osteoporosis and its underlying molecular mechanism remains unclear. The in vitro model of osteoporosis was established after bone marrow mesenchymal stem cells (BMSCs) were exposed to dexamethasone (DEX). The cell viability, alkaline phosphatase (ALP) activity and mineralized nodules of BMSCs were evaluated. The messenger RNA and protein levels were detected by quantitative real-time polymerase chain reaction and Western blot. The interaction between TERC, enhancer of zeste homolog 2 (EZH2) and dickkopf-1 (DKK1) was confirmed by chromatin immunoprecipitation and RNA immunoprecipitation assays. Bone marrow mesenchymal stem cells were isolated, identified and induced osteogenic differentiation. The findings showed that the levels of osteogenic marker genes, including ALP, Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) in BMSCs were increased dependent on the osteogenic induction time. Similarly, TERC was significantly increased, but DKK1 was significantly decreased during BMSC osteogenic differentiation. Functional research showed that TERC overexpression promoted cell viability, ALP activity and mineralized nodules of BMSCs and increased the levels of osteogenic differentiation-related genes (ALP, RUNX2 and OCN), and TERC overexpression increased EZH2 protein level. Moreover, the decrease of cell viability, ALP activity and mineralized nodules induced by DEX was reversed by TERC overexpression. Furthermore, TERC inhibited DKK1 expression by promoting the histone modification of DKK1, and TERC overexpression alleviated DEX suppressed osteogenic differentiation of BMSCs by interaction with EZH2 to regulate DKK1. Our findings illustrated that TERC overexpression alleviated DEX-induced osteoporosis by recruiting EZH2 to regulate DKK1. Our research provided a novel direction for the treatment of glucocorticoid-induced osteoporosis.

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

A Novel Role for RILP in Regulating Osteoclastogenesis and Bone Resorption

Increased bone resorption caused by excessive number or activity of osteoclasts is the main cause of osteoporosis. Osteoclasts are multinucleated cells that are formed by the fusion of precursor cells. Although osteoclasts are primarily characterized by bone resorption, our understanding of the mechanisms that regulate the formation and function of osteoclasts is poor. Here we showed that the expression level of Rab interacting lysosomal protein (RILP) was strongly induced by receptor activator of NF-κB ligand in mouse bone marrow macrophages. Inhibition of RILP expression induced a drastic decrease in the number, size, F-actin ring formation of osteoclasts, and the expression level of osteoclast-related genes. Functionally, inhibition of RILP reduced the migration of preosteoclasts through PI3K-Akt signaling and suppressed bone resorption by inhibiting the secretion of lysosome cathepsin K. Treatments with siRNA-RILP attenuated pathologic bone loss in disease models induced by lipopolysaccharide. Thus, this work indicates that RILP plays an important role in the formation and bone resorption function of osteoclasts and may have a therapeutic potential to treat bone diseases caused by excessive or hyperactive osteoclasts.

Efficacy of zoledronate, denosumab or teriparatide in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: protocol of an open, blinded endpoint randomized controlled pilot trial.

People with type 2 diabetes (T2D) are at high risk of fragility fractures; however, there are no randomized controlled trials evaluating the efficacy of anti-osteoporosis drugs as a primary pre-specified endpoint in T2D. To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D. Prospective, randomized, open, blinded endpoint clinical pilot trial. Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m2 and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 and high FRAX score will be eligible for inclusion. Subjects with secondary causes of osteoporosis, prior exposure to bone-active therapies or history of use of glucocorticoids/pioglitazone/thiazides/canagliflozin will be excluded. Finally, eligible subjects will undergo estimation of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone turnover markers (BTMs) (total procollagen type I N-propeptide, β-CTX) along with trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of non-dominant hand and leg. After a 2-week run in phase, they will be randomized in a 1:1:1:1 ratio to receive yearly zoledronate, or biannually denosumab or daily teriparatide (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary endpoints will be change in areal BMD and frequency of incident fractures at 18 months. The secondary endpoints will be change in HR-pQCT parameters, TBS and BTMs at 18 months. Adverse events will be recorded for all randomized participants. The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant. The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility. Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).

Alendronate functionalized PLGA based nanoparticles for the effective treatment of osteoporosis-Formulation to in-vitro release kinetic studies

Osteoporosis is a bone disease caused due to the reducing bone mineral density. Porous and more fragile bones increase the risk of fractures. Hip, spine, shoulder, and wrist bones are commonly affected by osteoporosis. Low bone density is a leading cause of osteoporosis. The most efficient prescribed drugs for the treatment of osteoporosis are bisphosphonates drugs. Alendronate was the first FDA approved bisphosphonate drug for the treatment of osteoporosis. Osteoclast cells are the primary targeting site for alendronate, responsible for bone resorption. A biopharmaceutical classification system class III bisphosphonate acts as a potent, efficient, and bone resorption inhibitor drug. In the present study, alendronate functionalized PLGA based nanoparticles were developed by a solvent diffusion method and optimized for different process variables. The formulated nanoparticles were characterized for surface morphology, particle size distribution, surface charge and drug-polymer compatibility. The scanning electron microscopy and transmission electron microscopy results showed nanoparticle size in the range below 200 nm. The average particle size and zeta potential of the formulated nanoparticles were found to be 175.3 nm and -13.98 mV, respectively. The highest encapsulation efficiency was 65.23%. The release profile was dissolution medium dependent and followed by the Higuchi model of release kinetics.