Improve Bone Density Research Articles

Bifidobacterium improves oestrogen-deficiency-induced osteoporosis in mice by modulating intestinal immunity.

Osteoporosis has become one of the major diseases that threaten the health of middle-aged and elderly people, and with the growth of an ageing population, more and more people are affected by osteoporosis these days. In recent years, intestinal flora has been found to affect the host immune system, and an overactive immune system is closely related to bone resorption. Probiotics can effectively improve bone density and strength, reduce bone loss, and improve osteoporosis, but their mechanism of action and relationship with intestinal microbiota are still unclear. In this study, two strains of Bifidobacterium (Bifidobacterium bifidum FL228.1 and Bifidobacterium animalis subsp. Lactis F1-7) that can alleviate intestinal inflammation were screened based on previous experiments. Through the construction of an ovariectomized mouse model, the improvement of osteoporosis by Bifidobacterium was detected, and the influence of Bifidobacterium on intestinal immunity was explored. The results show that Bifidobacterium treatment significantly improved bone mineral density (BMD), bone volume/total volume ratio (BV/TV), and trabecular number (Tb·N), and effectively suppressed bone loss. Furthermore, Bifidobacterium treatment could inhibit the expression of inflammatory cytokines in the gut, alleviate gut inflammation, and thus suppress excessive osteoclast generation. Its mechanism of action includes factors that protect the mucosal barrier, including occludin, ZO-1, claudin-2, and MUC2, and the reduction of pro-inflammatory M1 macrophages. B. bifidum FL228.1 increased the abundance of beneficial bacteria in the colon, including Lactobacillus and Colidextribacter. B. animalis F1-7 increased the abundance of Bifidobacterium and decreased the abundance of Desulfovibrio and Ruminococcus in the colon. These research findings expand our understanding of the gut-bone axis and provide new guidance for the development of probiotic-based therapies for osteoporosis in the future.

Impact of a bone health protocol on adult lung transplant recipients

Corticosteroids are a critical component of immunosuppressive regimens following lung transplantation; however, their use is associated with known deleterious effects on bone health. Protocolized preventative therapies and screening may improve bone health in this population. We retrospectively reviewed all adult lung transplant recipients (LTRs) at a single center before and after implementation of a bone health protocol. Fifty-eight LTRs were included; 38 pre-protocol and 20 post-protocol. Significant differences were noted for patients following a bone health protocol including dual x-ray absorptiometry (DEXA) completion (16 % vs. 70 %, p = <0.001), less significant decline in femur Z- and T-scores (p = 0.05 and 0.04, respectively), and were more likely to be prescribed anti-resorptive therapy (11 % vs 40 %, p = 0.008) and calcium therapy (24 % vs. 70 %, p = <0.001). Incidence of non-procedural fracture at two years was numerically lower in the post-protocol group (21 % vs. 15 %, p = 0.58). Our data suggests that institution of a bone health protocol for lung transplant recipients improves screening, bone health pharmacotherapy, improved bone density as measured by DEXA and may reduce risk of clinically significant fractures at two years post-transplant.

Parathyroidectomy Improves Bone Density in Women With Primary Hyperparathyroidism and Preoperative Osteopenia.

Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. Referral center. A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. Parathyroidectomy. BMD change between before and 1 year after parathyroidectomy. Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.

Water Extract of Desalted Salicornia europaea Inhibits RANKL-Induced Osteoclast Differentiation and Prevents Bone Loss in Ovariectomized Mice

Osteoporosis, which is often associated with increased osteoclast activity due to menopause or aging, was the main focus of this study. We investigated the inhibitory effects of water extract of desalted Salicornia europaea L. (WSE) on osteoclast differentiation and bone loss in ovariectomized mice. Our findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as demonstrated by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. The expression levels of genes related to osteoclast differentiation, including NFATc1, ACP5, Ctsk, and DCSTAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoylquinic acids (DCQAs) and saponins were detected in WSE, with 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA being isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQAs, as preventive or therapeutic agents against osteoporosis and related conditions.

Proteomic Analysis Based on TMT Regarding the Therapeutic Action of Rhizoma Drynariae on Rats in an Osteoporosis Model.

Primary osteoporosis has increasingly become one of the risk factors affecting human health, and the clinical effect and action mechanism of traditional Chinese medicine in the treatment of primary osteoporosis have been widely studied. Previous studies have confirmed that in traditional Chinese medicine (TCM), Drynaria rhizome has a role in improving bone density. In this study, a tandem mass tag (TMT)-based proteomic analysis was conducted to derive potential targets for Drynaria rhizome treatment in postmenopausal osteoporosis. The model group (OVX) and experimental group (OVXDF) for menopausal osteoporosis were established using the universally acknowledged ovariectomy method, and the OVXDF group was given 0.48g/kg Rhizoma Drynariae solution by gavage for 12 weeks. After 12 weeks, femurs of rats selected for this study were examined with a bone mineral density (BMD) test, Micro-CT, ELISABiochemical testing, hematoxylin and eosin (HE) staining, and immunohistochemistry. A certain portion of the bone tissue was studied with a TMT-based proteomic analysis and functional and pathway enrichment analysis. Finally, key target genes were selected for Western blotting for validation. The comparison of the OVXDF and OVX groups indicated that Drynaria rhizome could improve bone density. In the TMT-based proteomic analysis, the comparison of these two groups revealed a total of 126 differentially expressed proteins (DEPs), of which 62 were upregulated and 64 were downregulated. Further, by comparing the differential genes between the OVXDF and OVX groups and between the OVX and SHAM groups, we concluded that the 27 differential genes were significantly changed in the rats selected for the osteoporosis model after Drynaria rhizome intragastric administration. The gene ontology (GO) enrichment analysis of DEPs showed that molecular function was mainly involved in biological processes, such as glucose metabolism, carbohydrate metabolism, immune responses, and aging. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEPs revealed that multiple differential genes were enriched in the estrogen and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Relationships with nitrogen metabolism, glycerophospholipid metabolism, secretion systems, and tumor diseases were also observed. Western blotting was consistent with the analysis. We used TMT-based proteomics to analyze the positive effects of TCM Drynaria rhizome, which can regulate related proteins through the unique roles of multiple mechanisms, targets, and pathways. This treatment approach can regulate oxidative stress, improve lipid metabolism, reduce the inflammatory response mechanism, and improve bone density. These benefits highlight the unique advantages of TCM in the treatment of primary osteoporosis.

Potential of molecular biophysical stimulation therapy in chronic musculoskeletal disorders: a narrative review.

Current treatment of chronic musculoskeletal diseases does not give sufficient results despite the implementation of novel drugs and techniques in orthopaedics and physical therapy. For instance, osteoporosis treatment is currently mainly limited to drug application, while the goal of osteoarthritis treatment is to mitigate pain symptoms through physical therapy. The main therapeutic principle in the management of osteoporosis is not only to increase bone mass, but also to improve bone and the cartilage quality, which depends on the biomechanical balance. Therefore, there is a strong demand for advanced technologies that would safely and non-invasively accelerate cartilage regeneration and improve bone density. Ten years ago, a new state-of-the-art technology - "Molecular biophysical stimulation therapy (MBST)", specifically nuclear magnetic resonance therapy, emerged on the medical technology market and until now, it has shown successful results in the conservative treatment of musculoskeletal disorders, including back pain. The aim of this review is to provide an integrated, synthesized overview of the current evidence of efficacy of MBST for managing chronic musculoskeletal disorders.

Impact of diversified aerobic training approaches for amplifying bone density in young individuals

Various aerobic training approaches have garnered considerable interest in improving bone health in young individuals. This study examines the effects of high-impact and low-impact multi-aerobic training on bone density in healthy young students in an effort to enhance bone health. In this study, the primary objective is to assess the effects of diverse multi-aerobic training regimens on bone density among 20-25 year olds. This study also examines the benefits of integrating high-impact and low-impact exercises for improving bone health. We selected 120 participants (60 men and 60 women) for a 27-week randomized three-by-two experimental design. Three groups of participants were assigned to each exercise group: the high-impact group (HIEG), the low-impact group (LIEG), and the control group (CG). A bone density (BD) measurement was performed before and after the training program using dual-energy X-ray absorptiometry (DXA). The results of an ANCOVA with baseline scores as covariates indicated a significant improvement (P &lt; 0.05) in bone density among participants following the intervention. As compared to CG, both HIEG and LIEG improved bone density significantly (P &lt; 0.05), suggesting multi-aerobic training promotes bone health effectively. It highlights the potential of both HIEG and LIEG in enhancing bone density in young individuals through a 27-week diversified multi-aerobic training program. In order to cultivate and enhance bone density among young individuals, regular multi-aerobic exercise is critical to their lifestyles. This can be used to formulate exercise interventions aimed at boosting bone health in both sexes.

Regular sling core stabilization training improves bone density based on calcium and vitamin D supplementation

BackgroundPrimary osteoporosis refers to a disease of aging characterized by reduced bone mass, damage to bone tissue microarchitecture, and predisposition to fracture.Sling core stabilization training emphasizes activating the deep local muscles of the spine under unstable conditions, and enhancing the body’s balance and control during exercise.Case presentationA 70-year-old female went to the Acupuncture and Rehabilitation Department due to low back pain caused by osteoporosis.The patient received sling core stabilization training three times a week based on Calcium and Vitamin D Supplementation. After training, the patient’s back pain was significantly relieved and insisted one year. In the physical examination of bone mineral density, the results showed that the value of bone mineral density was better than last year.The patients adhered to sling core stabilization training and observed the changes of bone mineral density every year basis on calcium and vitamin D supplementation.DiscussionHowever, cases of calcium and vitamin D supplementation-based regular sling core stabilization training that improves bone density in osteoporosis patients have been rarely reported. Our group shared cases and analyzed possible mechanisms, hoping to provide reference for the prevention and treatment of primary osteoporosis.

THU451 Low Bone Mineral Density In A Patient With Thalassemia Minor

Abstract Disclosure: F. Woron: None. P. Madhavan: None. Osteoporosis is a known complication of thalassemia major and thalassemia intermedia, but is not typically considered in patients with thalassemia minor. Here, we present a 74-year-old Caucasian male patient with thalassemia minor who presented to us for follow-up of osteoporosis. The patient reports a history of osteoporosis that was diagnosed prior to 2004. Additionally, he has a history of radiation exposure to his head and neck, goiter, prostate cancer status post resection in 2019, and atrial fibrillation, for which he has been on apixaban since 2021. He was treated with risedronate for his osteoporosis from approximately 2004 to about 2011 by other providers, with improvement in bone density to osteopenia. Free testosterone, parathyroid hormone, calcium, and serum protein electrophoresis levels evaluated prior to his diagnosis of osteoporosis were all noted to be normal. He has not had a fracture as an adult. He is being monitored with conservative management and currently aims for a daily calcium intake of 1000-1200 mg, including diet and supplements, and a daily Vitamin D intake of 2000 IU. He engages in frequent weight-bearing exercise. As of September 2021, his bone mineral density was osteopenic in the lumbar spine (T score of −2) and left hip (total T score of the left hip −1.6, and −1.8 in the femoral neck). The patient had no other known risk factors for decreased bone mineral density preceding the onset of his osteoporosis, and a previous workup for secondary causes of his osteoporosis etiology proved negative. Adding to one existing case report in the literature, we propose that thalassemia minor may potentially be a risk factor for osteopenia and osteoporosis, and that we should consider screening thalassemia minor patients with DXA for evaluation of bone health. Presentation: Thursday, June 15, 2023

SAT668 Can We Treat Osteoporosis, Obesity And Neurodegeneration With A Single FSH-blocking Drug?

Abstract Disclosure: A.R. Pallapati: None. J. Gimenez-Roig: None. S. Rojekar: None. F. Korkmaz: None. D. Sant: None. O. Barak: None. F. Sultana: None. O. Moldavski: None. A. Gumerova: None. H.S. Kannangara: None. U. Cheliadinova: None. C.J. Rosen: None. J.N. Caminis: None. M. Meseck: None. V.E. Demambro: None. S.L. Sims: None. S. Gera: None. R. Witztum: None. S. Miyashita: None. V. Ryu: None. M. Saxena: None. T. Frolinger: None. A. Macdonald: None. S. Kim: None. G. Pevnev: None. D. Lizneva: None. T. Yuen: None. M. Zaidi: None. Pharmacological and genetic studies suggest that FSH is an actionable target for diseases affecting millions, notably osteoporosis, obesity and Alzheimer’s disease (AD). Blocking FSH action prevents bone loss (1, 2), fat accrual (3) and AD-like features in mice (4). We recently developed a first-in-class, humanized, epitope-specific FSH blocking antibody that binds to a 13-amino-acid-long sequence of FSHβ—MS-Hu6—with a KD of 7.52 nM (5). We showed that MS-Hu6 binds specifically to FSHβ, without binding to LH and TSH. For efficacy studies, we have blocked FSH action using either MS-Hu6 or the parent murine antibody, Hf2, targeted to the same epitope. Using our Good Laboratory Practice platform (Code of Federal Regulations, Title 21, Part 58), we report that FSH blockade prevents obesity, osteoporosis and AD in mice. We injected 20-week-old C57BL/6 male mice on a high-fat diet with a range of doses of Hf2 or vehicle s.c. five-days-a-week for 8 weeks. Hf2 (100 µg/mouse/day) reduced the increase in fat mass by 33% starting week 3, with a 7% reduction in in body weight. In separate studies, MS-Hu6 not only caused beiging of white adipose tissue in UCP1-reporter ThermoMice (IVIS imaging), but also improved bone density and microstructure (micro-CT) by elevating bone formation (dynamic histomorphometry). The increase in bone mass and improved microstructure were replicated in Cliff Rosen’s lab using C57BL6 mice 24 weeks post-ovariectomy. Novel Object Recognition testing of AD-prone, ovariectomized 3xTg mice showed a deficit in recognition memory, which was reversed after 8 weeks of Hf2 (100 µg/mouse/day for 5-days-a-week) exposure. Biodistribution studies using 89Zr-labelled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone, bone marrow, fat depots and brain tissue. MS-Hu6 displayed a β phase t½ of 7.5 days in humanized Tg32 mice. In monkeys, an acute single injection of MS-Hu6 did not affect vitals, and biochemical parameters remained within the normative range. We tested 215 variations of excipients using a range of physicochemical techniques, including protein thermal shift, size exclusion chromatography, dynamic light scattering, Fourier-transform infrared spectroscopy, circular dichroism spectroscopy, and differential scanning calorimetry, to yield a formulation with thermal, colloidal, monomeric and structural stability at an ultra-high concentration (100 mg/mL) with acceptable viscosity, clarity and turbidity parameters. MS-Hu6 showed the same “humanness” as human IgG1 in silico and was non-immunogenic in ELISPOT assays for IL-2 and IFNγ in human PBMC cultures. In conclusion, MS-Hu6 is efficacious, durable and manufacturable, and is therefore poised for human testing as a multipurpose therapeutic for obesity, osteoporosis, and perhaps for AD. 1Cell, 2006; 2PNAS, 2018,; 3Nature, 2017; 4Nature, 2022; 5. PNAS, 2020, eLife, 2022. Presentation: Saturday, June 17, 2023

Correlation of Vitamin D and Core Stabilization Exercise in Low Back Pain: A Narrative Review

Background and Aim: Low back pain is a complex condition that can have various causes and its management involves multiple treatment strategies as per the cause. Use of vitamin D supplementation for LBP has gained attention due to its anti-inflammatory effect and helps to improves bone density whereas core stabilization exercises can help to strengthen core and spinal muscles and stabilize the spine. While there is evidence to suggest that both Vitamin D and core stabilization exercise may have potential benefits for low back pain, the direct correlation between these two factors is not well established. So the aim of this narrative review is to find out the correlation of Vitamin D and Core Stabilization exercise in low back pain. Methods: We searched the articles using PubMed and Google Scholar regarding the correlation of Vitamin D and Core Stabilization exercise in male and female low back pain subjects. Results: Evidence from human studies suggest that Vitamin D and core stabilization exercises both are important for overall functioning of intervertebral disc integrity and its stability. Vitamin D is a vital nutrient that plays a critical role in maintaining bone health, regulating the immune system, and reducing inflammation whereas Core stabilization exercises improves core and spinal muscle strength that stabilizes the spine. Conclusions: Clinicians caring for patients must be aware of this Vitamin D and Core stabilization exercises to find the right treatment course for each patient. In many cases quick Vitamin D supplementation along with Core stabilization exercises may be used to manage LBP. While there is a rightful role for Vitamin D in management of lumbar low back pain, non-pharmacological options like Core stabilization exercises should also be considered as they can play an important role in physiotherapy management of low back pain.

Utilization of Low-Magnitude High-Frequency Vibration (LMHFV) as an Aid in Treating Peri-Implantitis: Case Presentations.

Peri-implantitis is an inflammatory process initiating in the soft tissue and then progressing to the hard tissue surrounding dental implants leading to loss of osseous support and potential loss of the implant if not identified early in the process. This process initiates in the soft tissue, which become inflamed spreading to the underlying bone leading to decreases in bone density with subsequent crestal resorption and thread exposure. In the absence of treatment of the peri-implantitis, the bone loss at the osseous implant interface progresses with inflammatory mediated decrease in the bone density that moves apically, eventually leading to mobility of the implant and its failure. Low-magnitude high-frequency vibration (LMHFV) has been shown to improve bone density, stimulate osteoblastic activity, and arrest progression of peri-implantitis with improvement of the bone or graft around the affected implant with or without surgery as part of the treatment. Two cases are presented using LMHFV to augment treatment.

Effect of Growth Hormone and Estrogen Replacement Therapy on Bone Mineral Density in Women with Turner Syndrome: A Meta-Analysis and Systematic Review.

Osteoporosis is a serious implication of Turner syndrome (TS). Common methods for the treatment of TS are growth hormone (GHT) and estrogen replacement therapy (ERT). We examined the relationship between the treatment of TS and bone mineral density (BMD) of the lumbar spine. The purpose of our study was to show the currency of BMD states among patients with TS for treatment with GHT and ERT. We searched databases for studies published from inception to April 2023. The articles were related to TS, osteoporosis, ERT, GHT, BMD and treatment patients with TS. We applied the selection criteria: lumbar spine values at L1-L4; dual-energy X-ray absorptiometry (DXA); treatment which was applied: one group of articles: ERT and two group of articles: GHT; results performed as means ± SD. In total, 79 articles were analyzed, of which 20 studies were included and 5 were considered for meta-analysis. The total number of women in the articles selected was 71. Based on the results of the meta-analysis, the effect of ERT on BMD demonstrated a significant increase in BMD (the standardized mean difference in the random model was 0.593 g/cm2, 95% CI: 0.0705 to 1.116; p = 0.026), which showed that treatment with estrogen particularly increases bone mass during treatment, which contributes to reducing the risk of fractures. The effect of GHT on BMD demonstrated a non-significant decrease in BMD in patients with TS. The results for growth hormone show that this therapy does not improve bone density. However, our review emphasizes the beneficial effect of supplementing growth hormone (GH) on the clinical presentation of TS.

Tenofovir disoproxil fumarate versus tenofovir alafenamide on risk of osteoporotic fracture in patients with chronic hepatitis B: A nationwide claims study in South Korea.

As tenofovir disoproxil fumarate (TDF) requires long-term use, a reduction in bone density should be considered a possibility when treating patients with chronic hepatitis B (CHB) with aging and systemic diseases. Patients treated with tenofovir alafenamide (TAF) have improved bone mineral density loss compared to patients treated with TDF. Although improvements in bone density caused by TAF have been reported, studies on the actual reduction of fractures are insufficient. To evaluate the impact of TAF on the risk of osteoporotic fractures in comparison with that of TDF. Using the national claims data of the Health Insurance Review and Assessment Service, we conducted a retrospective cohort study of 32,582 patients with CHB who had been initially treated with TDF or TAF between November 2017 and December 2020. The numbers of patients treated with TDF and TAF were 20,877 and 11,705, respectively. The annual fracture rate per 100 patients in each group was calculated, and the Cox proportional hazard ratio (HR) was analysed after applying inverse probability treatment weights (IPTW) for both groups. Among 32,582 patients, the average age was 47.8 ± 11.2 years, 64.5% were men, and the follow-up period was 24.4 ± 11.6 months. The incidence of osteoporotic fractures was 0.78 and 0.49 per 100 person-years in the TDF and TAF groups, respectively. After application of IPTW, the HR was 0.68 (95% confidence interval 0.55-0.85, p = 0.001). TAF-treated patients with CHB had a significantly lower risk of osteoporotic fracture than TDF-treated patients.

Non-traditional HIIT-style ROTC training elicits positive bone quality and performance adaptations

ABSTRACT Military personnel experience elevated bone injury incidence, partly due to arduous and repetitive training. Non-traditional High-Intensity Interval Training-style (HIIT) may benefit pre-enlisted Reserve Officer Training Corps (ROTC) cadet’s musculoskeletal health and performance prior to military service. This study investigated 16 ROTC (n = 12 males; n = 4 females) and 15 physically active sex-, age-, and body mass-matched Controls’ musculoskeletal health and performance from November to April. Total body, lumbar spine, and dual- hip dual-energy X-ray absorptiometry scans and 4%, 38%, 66% tibial peripheral quantitative computed tomography scans, blood draws (serum sclerostin and parathyroid hormone), and maximal muscle strength and aerobic capacity testing were completed. From November to April, ROTC improved bone density (DXA) of the dominant total hip and greater trochanter and non-dominant greater trochanter and 38% and 66% tibial total volumetric and cortical bone density (pQCT) similarly or more than Controls (all p ≤ 0.049). From November to April, ROTC also improved bench and leg press, and peak aerobic capacity (all p ≤ 0.013). From November to January, serum sclerostin increased (p ≤ 0.007) and remained elevated through April, while parathyroid hormone was unchanged. HIIT-style training induced positive musculoskeletal adaptations, suggesting it may be an excellent pre-service training modality for this injury prone group.

Discovery of an orally effective double-stapled peptide for reducing ovariectomy-induced bone loss in mice.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts invitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Efficacy of antiresorptive agents in fibrous dysplasia and McCune Albright syndrome, a systematic review and meta-analysis.

Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI95% -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI95% -31.9, -12.1] in the parameters of bone formation after 6-12months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI95% -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI95% -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R2 = 0.08, p < 0.0001) and formation parameters (R2 = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.

Association ofbisphosphonate with bone loss andpain-related behaviour inan adjuvant-induced osteoporosis model.

Osteoporosis animal models are used extensively to determine the mechanisms of disease pathology and identify potential biological targets. The study aimed to establish a bone loss model, identify pain-related behaviour in neighbouring joints using an adjuvant-induced osteoporosis model, and examine the therapeutic effect of bisphosphonates. Complete Freund's adjuvant was injected subcutaneously into the back of the right foot of 8-week-old female ddY mice. Subsequently, pain, arthritis, and bone density in the right knee were monitored over time. Pain evaluation using von Frey filaments showed a significantly exacerbated knee pain threshold compared to the control group (saline administration) at 7- and 14-day intervals after complete Freund's adjuvant administration, and bone density during the same period also significantly declined. The adjuvant-induced osteoporosis model was created similarly; alendronate 40 μg/kg was subcutaneously injected twice and vehicle once from 7 to 14 days after onset. In the alendronate administration group on the 14th day, significant improvements in bone density, arthritis, and pain threshold around the knee were observed compared to the untreated group. Alendronate may contribute to pain improvement through the simultaneous effects of bone mass improvement and suppression of osteoporotic pain.

A Bone Targeting Nanoparticle Loaded OGP to Restore Bone Homeostasis for Osteoporosis Therapy.

Restoring bone homeostasis is the key to the treatment of osteoporosis. How to increase osteogenic ability or inhibit osteoclast activity has always been a topic of great concern. In recent years, short peptides with biological activity have received great attention in bone repair. However, the application of short peptides is still limited due to the lack of a stable and targeted delivery system. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified by alendronate (AL) to transport osteogenic peptides (OGP) (AL-PLGA@P NPs) are designed. Benefiting from the high affinity of AL for hydroxyapatite, AL-PLGA@P NPs have the ability to target bone. In this delivery system, OGP that promotes osteogenesis synergizes with AL, which inhibits osteoclasts, to regulate bone homeostasis, which gives them more advantages in the treatment of osteoporosis. The data shows that nanoparticles can selectively deliver peptides to the bone surface without systemic toxicity. Moreover, nanoparticles can upregulate osteogenesis-related factors (ALP, Runx-2, and BMP2) and downregulate osteoclast-related factors (TRAP and CTSK) in vitro. With AL-PLGA@P NPs, bone microarchitecture and bone mass are improved in ovariectomized osteoporosis rats. Therefore, this study proposes a novel osteoporosis-based drug system that effectively improves bone density.

Vitamin D supplementation for improving bone density in vitamin D–deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials

BackgroundVitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D–deficient children are unclear. ObjectivesThis study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D–deficient individuals. MethodsThis is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1–19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. ResultsEleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. ConclusionsClinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets).This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772