Osteoporosis can cause chronic pain, but the mechanisms are unclear. This study investigates pain behaviours in mouse models of osteoporosis and fracture together with nociceptive markers expression in bone and dorsal root ganglia (DRGs). It also quantifies nerve markers in serum of patients with or without osteoporotic fractures and pain. Ovariectomy (OVX) or Sham surgery (Sham-OVX) of C57/Bl6 mice was performed (n = 10/group) and evoked and spontaneous pain behaviours assessed. In another experiment, OVX or Sham-OVX mice underwent a femoral osteotomy or sham osteotomy (n = 8/group) and pain behaviours measured. Gene expression of pain markers in bone and DRGs was quantified by RT-PCR. Nerve markers were quantified in serum of osteoporotic patients with or without fractures and pain using specific ELISAs. OVX did not cause changes in pain behaviours nor alter nociceptive gene expression in bone and DRGs. Osteotomy and Sham osteotomy both affected pain behaviours in mice compared to non-operated controls but did not significantly change nociceptive gene expression in bone and DRGs. OVX before osteotomy worsens weight-bearing compared to Sham-OVX. Fracture and pain did not affect nerve markers expression levels in serum of osteoporotic patients. This study demonstrates that OVX and subsequent bone loss in mice are insufficient to induce pain behaviours but may intensify pain after fracture. Our clinical analysis does not show a correlation between circulating nerve markers and fracture pain reported by the patients but suggests possible sex differences in pain markers that need to be further investigated.

BackgroundDementia represents a significant health and societal challenge, identified as a primary cause of mortality worldwide and closely associated with the aging population. A 24‐year follow up study indicated that socioeconomic status affects the risk of multimorbidity including dementia, frailty, and disability, with multimorbidity showing the strongest association with mortality. There is evidence that fractures pose a risk factor for dementia and individuals with dementia had a higher risk for falls and fractures. The common risk factors for dementia and impaired bone health are aging, ApoE 7, vitamin D and lifestyle choices. To determine if there are global changes in bone health along the progression of AD, we performed a cross‐sectional evalution of serum levels of proteins related to bone metabolism.MethodsPlasma from people wiht Alzheimer's disease (AD, n = 95), Mild cognitive impairment (MCI, n = 134), and healthy controls (HC, n = 394) was used to extract plasma proteins. 2865 proteins were identified after heparin‐bound proteins were enriched using heparin affinity chromatography and subsequently subjected to tandem mass spectrometry at Stanford ADRC, followed by filtering for bone markers.ResultsIn MCI, Collagen A1(VI), WNT16, and OLR1 are upregulated in males whereas IGFBP‐1, Ephrin‐A2, and IGFBP‐1 are downregulated compared to HC. In females, COL is downregulated in MCI compared to HC. On the other hand during AD, bone related proteins Collagen A1(VI) and CHST6 are upregulated in males, whereas FGF‐19, IGFBP‐1, Chondrocalcin, FGF‐19, and IGFBP‐1 are downregulated compared to HC. In females, FGF‐19 is upregulated and IGFBP‐1 and COL are downregulated in AD compared to HC. The senescent markers upregulated in MCI are WNT16 and HGFm whereas IL32 in AD compared to AD patients.ConclusionsThese findings provide evidence of sex‐dependent progressive bone tissue alterations, and plasma biomarkers of senescence revealing a potential link between age associated neurodegeneration and bone health.

Background Osteoarthritis is multifactorial joint disorder marked by the progressive breakdown of articular cartilage, alterations in the underlying subchondral bone, and chronic inflammation of the synovial membrane. Objective To measure serum levels of bone biomarkers (osteocalcin and sclerostin) in osteoarthritis patients as compared to healthy controls and also to find out the link of these biomarkers with proinflammatory cytokines including IL-6, IL-17, IL-1β and TNF-α. Materials and methods A case-control study was implemented on 65 osteoarthritis patients and 35 healthy controls participants. Blood samples were taken from participants after obtaining written informed consent. Serum levels of cytokines and bone markers were measured using ELISA. Pain disability and intensity were measured using the "Chronic Pain Grade questionnaire". Results Compared to controls, patients with osteoarthritis had significantly higher levels of IL-1β, TNF-α, IL-6, and IL-17 (P < 0.0001 for all). Osteocalcin levels were dramatically lower in the osteoarthritis group than the controls (mean ± SD: 23.50 ± 19.30 ng/mL vs. controls 48.90 ± 5.20 ng/mL), while sclerostin levels were much higher (11.70 ± 1.10 ng/mL in osteoarthritis vs. 3.80 ± 0.90 ng/mL in controls, P < 0.0001). Osteocalcin showed a moderate positive correlation with IL-17, IL-6, and TNF-α; sclerostin showed a negative correlation with these cytokines. Discussion A strong positive correlation exists between osteocalcin and proinflammatory interleukins. The downregulation of sclerostin in OA also shares common pathways with proinflammatory cytokines that drive expression of osteocalcin. Inflammation results in osteocyte apoptosis or their dedifferentiation, and this further lowers the population of sclerostin-secreting cells in the subchondral bone. This is how the reverse correlation is explained between sclerostin and proinflammatory cytokines in OA. Conclusions Results show a robust inflammatory-bone axis in the pathogenesis of osteoarthritis. High proinflammatory cytokines might bring about osteocalcin expression and also inhibit sclerostin, leading to pathological subchondral bone alteration. These biomarkers reflect disease activity and therefore could be used for early detection as well as monitoring and phenotypic stratification of osteoarthritis.

Background/Objectives: This 8-week randomized pilot intervention trial examined the effects of Greek yogurt (GY) supplementation on markers of bone turnover and inflammation in older adult exercisers. Methods: A total of 48 participants aged 55+ completed this 8-week intervention: 33 exercisers randomized to exercisers receiving GY (GYEX, n = 18, 12 females) and exercisers without GY (NYEX, n = 15, 12 females), and a group of 15 age-matched, community-dwelling, non-exercisers also receiving GY (GYNE, n = 15, 10 females). Exercisers were enrolled in a moderate-intensity community-based exercise program. GYEX and GYNE supplemented their diet with two daily servings of 175 g of GY (17 g protein, 225 mg calcium per serving). Assessments at baseline and week 8 included dietary intake, body composition, and fasting blood samples for bone markers and pro-inflammatory cytokines. Results: Body mass increased modestly across groups (time effect, p = 0.033), with no changes in body fat. C-terminal telopeptide of type I collagen (bone resorption marker) increased 14% in GYEX (time × group interaction, p = 0.022). Osteoprotegerin (bone formation regulator) decreased overall by 4% (time effect, p = 0.002). Dickkopf-1 (bone formation inhibitor) increased by 13% (p = 0.008) in GYNE but not in exercisers (time × group interaction, p = 0.018). Interleukin 1β and interleukin 6 showed significant interactions (p = 0.043 and p = 0.023), where interleukin 1β increased by 80% (p = 0.007) and interleukin 6 decreased by 89% (p < 0.001) in GYNE, but remained stable in exercisers. Tumor necrosis factor alpha remained unchanged. Conclusions: Although the observed effects of GY on the assessed biomarkers were limited and should be interpreted cautiously due to pilot design and statistical constraints, they highlight the need for longer interventions to determine whether whole-food dairy proteins can meaningfully support skeletal and immune health in older adults.

Computed tomography (CT) has become a valuable tool for preoperative planning and perioperative, real-time navigation during total hip arthroplasty (THA). CT can also quantify postoperative implant migration without the need for implanted bone markers, making it a promising alternative to the current gold standard radiostereometric analysis (RSA). Our aim was to evaluate the accuracy of preoperative planning and postoperative implant migration of both cup and stem employing AI-based software using 3D CT-images (CT-RSA) compared with conventional RSA. 26 patients with primary THA were preoperatively 3D-planned and perioperatively navigated. They were followed and analyzed with AI-based CT-RSA within 2 days postoperatively and at 3, 12, and 24 months. 10 of the patients had implanted tantalum markers at surgery and were also followed up with conventional model-based RSA (MBRSA). The results were compared with CT-RSA. Prosthetic CAD models were used for both conventional RSA and AI-based CT-RSA analysis. Double CT and MBRSA scans were taken to evaluate precision. The preoperative plan was compared with actual perioperatively chosen implants. AI-based CT-RSA showed consistent migration patterns, with most migration in the first 3 months, which then levelled out. Bland-Altman plots indicated good agreement between MBRSA and AI-based CT-RSA. Overall, there was high correspondence between MBRSA and AI-based CT-RSA in translations, but more divergent rotation results. AI-based CT-RSA precision was consistently slightly better than MBRSA precision. The agreement between planned and actual size of cup was 25 out of 26, and 23 out of 26 for stems. AI-based CT-RSA demonstrated accuracy comparable to MBRSA, with slightly improved precision and reduced user-dependence. The same system also provided an accurate and predictable preoperative implant plan.

ABSTRACTEarly post‐weaning growth is a critical window for bone development, and diet plays a central role in establishing peak bone mass in early life. Whey protein phospholipid concentrate (WPPC), a co‐product of whey protein isolate manufacturing, is enriched in bioactive lipids and proteins that may support bone development and calcium homeostasis. This study aimed to investigate the effects of WPPC and its protein‐ and lipid‐enriched fractions on bone development, gene expression, and gut microbiota in weanling mice. WPPC was fractionated using temperature‐dependent centrifugation, microfiltration, and ultrafiltration, yielding lipid‐ and protein‐rich components that were used to supplement isocaloric diets. Mice were fed either lipid fraction (Fat), protein fraction (Protein), or whole WPPC (WPPC) (10% by kcal; ~8.7% w/w) for 12 weeks. Compared to controls, the Protein and WPPC groups exhibited significantly increased femur length (4.44% and 4.01%, respectively), while the Fat group showed significantly higher bone mineral density (6.15%). Quantitative PCR of jejunal tissues revealed upregulation of calcium transporter genes (Cldn2, Cldn12, and Pmca1) in WPPC‐fed mice with no changes in vertebral bone markers of osteocyte differentiation. Circulating iFGF23 levels also remained unchanged, suggesting limited endocrine involvement. Gut microbiota analysis via 16S rRNA sequencing showed diet‐specific shifts, including increased Akkermansia and Streptococcus in the WPPC group and elevated Lactobacillaceae in the Protein and Fat groups. These findings demonstrate that WPPC and its enriched macronutrient fractions promote skeletal development and modulate calcium uptake and gut microbial composition, supporting their potential as functional ingredients for bone health applications in early life.

Impact of macrogeometry on the primary stability and bone markers of dental implants: A prospective, controlled, randomized, split-mouth clinical study.

Effects of mental disorders on the relationship between physical activity and bone markers among depressed patients in Germany

Bone Health and Body Composition as Predictive and Prognostic Markers in Metastatic Castration-resistant Prostate Cancer: A Meet-URO Narrative Review.

19 - Analysis of various parameters of electric current &amp; its effect on expression of bone markers and Osteosarcoma bone cells

Aqueous extract of Ormocarpum cochinchinense augments proliferation and promotes osteogenesis in osteoblast like MG63cells.

Type 2 diabetes (T2D) is associated with normal or higher bone mineral density (BMD), but there is a higher fracture rate. Hypoglycaemia does not affect BMD but may cause fractures directly through falls and may affect bone cellular metabolism. We examined circulating bone marker proteins (BMPs) in response to induced hypoglycaemia in T2D versus controls. A prospective exploratory parallel study design was conducted in T2D patients (n = 23) and healthy controls (n = 23) who underwent blood SOMAscan proteomic analysis of bone biomarkers at baseline, hypoglycaemia, and post-hypoglycaemia time points. Unadjusted repeated measures linear mixed modeling was used for analysis. Linear mixed modeling of the proteins showed that the way most BMPs changed over time did not differ between groups. At baseline, Dickkopf-related protein 1 (DKK1), cathepsin A, cathepsin S, and cathepsin Z were increased in T2D versus controls (p < 0.05), whilst fibroblast growth factor 23 (FGF23) was lower in T2D versus controls (p ≤ 0.05). Following hypoglycemia, transient changes from baseline occurred in DKK1, cathepsin A, cathepsin G, cathepsin H, cathepsin S, cathepsin Z, parathyroid hormone (PTH), Sphingosine kinase 1 and 2 (SPK1/2), and interleukin-1 beta (IL1 beta) over the post-hypoglycaemia time course. There was decreased cathepsin S in T2D from baseline to 24 h compared to the control group, and increased cathepsin Z at 24 h for both groups overall compared to baseline (p < 0.05). Baseline-raised cathepsins (A, S, Z) in T2D may enhance osteoclastic resorption, whilst raised DKK1 could inhibit osteoblast differentiation and suppress bone formation. Hypothetically, this may lead to a decline in bone quality through a resorption-enhanced, low bone formation imbalance. The effects of hypoglycaemia on bone physiology appear to extend significantly beyond the initial insult, as seen for cathepsin S and Z, which differed at 24 h compared to baseline.

Targeting the glucose dependent insulinotropic polypeptide receptor (GIPR) is of growing interest for treating type 2 diabetes and obesity, though the optimal approach remains unclear. Both GIPR agonism and antagonism, respectively, incorporated into drugs like tirzepatide and maridebart cafraglutide, have paradoxically both shown significant weight loss effects in humans. In this study, the metabolic impacts of a GIPR agonist (GIP108) and antagonist (NN-GIPR-Ant) were evaluated in lean and high-fat diet (HFD)-induced obese male mice. We assessed the impacts on food intake, body weight, glucose and insulin tolerance, liver triglyceride levels, bone markers and adipose tissue lipolytic gene expression. In lean mice, neither peptide affected food intake or body weight, but GIP108 improved glucose tolerance. In obese mice, both agents reduced food intake and body weight, with NN-GIPR-Ant producing more sustained appetite suppression. Energy expenditure remained unchanged, as weight loss matched that of pair-fed controls. GIP108 improved glucose tolerance independently of weight loss, whereas NN-GIPR-Ant reduced insulin sensitivity compared to pair-fed controls. Both treatments slightly increased liver triglyceride content compared to their pair-fed controls, and no treatment significantly affected plasma bone marker levels. Finally, NN-GIPR-Ant reduced the expression of adipose tissue lipolytic genes. Our data highlights the distinct metabolic effects of GIPR agonism and antagonism, offering insights for their future application in personalised metabolic disease treatments. Further human studies are needed to understand the long-term metabolic impacts of these therapies.

Background: The current study aimed to ascertain the impact of pulsed magnetic therapy, multicomponent exercise, and a combination of both modalities on bone markers type 2 diabetic patients with osteoporotic. Methods: In a randomized controlled clinical trial study, 56 older patients with type 2 diabetic osteoporosis (age: 68.18±3.67 yr; weight: 78.13±7.65 kg, body mass index: 28.40±1.76 kg/m2) were randomly assigned to either the multicomponent exercise + Full-body pulsed electromagnetic field (MCEx+PEMF, n= 18) multicomponent exercise + placebo full-body PEMF (MCEx+PPEMF, n=17) and a full-body PEMF alone (PEMF, n= 21). PEMF was applied for the whole body using a full-body mat three times per week, 60 minutes for 12 weeks, with a multicomponent exercise protocol that includes flexibility, aerobic exercise, strengthening, weight-bearing, and balance exercises followed by whole-body vibration (WBV) training. The body composition, bone mineral density (BMD), bone metabolism markers (phosphorus, calcium, sclerostin, osteocalcin, Bone-specific alkaline phosphatase (BALP)) before and after the intervention. The data were analyzed using the dependent t test and the two-way repeated measures ANOVA at the level of less than 0.05. Results: After 12 weeks of intervention, there is a significant difference in the serum levels of bone mineral density and bone metabolism markers (phosphorus, calcium, sclerostin, BALP) between the groups (P&lt; 0.05). However, the bonferoni post-test showed an increase in serum levels of BMD, phosphorus, sclerostin, BALP with a significant decrease in calcium in the MCEx+PEMF group in compared to alone PEMF group. Conclusion: The findings showed that the PEMF rehabilitation method combined with multicomponent exercise is more effective and safer than exercise or PEMF only for improving BMD and bone metabolism markers in the type 2 diabetic population with osteoporosis. Therefore, exercise rehabilitation clinics should be encouraged to consider exercise rehabilitation as a treatment method for type 2 diabetic patients with osteoporosis. More studies with long- term follow-up should be considered to confirm these findings

Alveolar bone defects in dentistry-caused by trauma, congenital anomalies, and periodontal disease-can substantially impair oral health and tooth function. These effects pose significant challenges in dentistry, and current gold-standard treatments such as autogenous bone grafting have notable limitations. Stem cell from human exfoliated deciduous teeth (SHED) has great potential for bone tissue engineering. The aim of this study was to evaluate the effect of SHED seeded in polymethylmethacrylate (PMMA)-hydroxyapatite (HA) scaffolds on the expression of osteogenic markers in alveolar bone defects.A total of 24 male Wistar rats had their maxillary incisors extracted, and the resulting defects were randomly assigned to three groups: (1) no treatment (control), (2) defects treated with PMMA-HA, and (3) defects treated with SHED seeded in PMMA-HA scaffolds. Immunoreactivity of BMP2, RUNX2, ALP, TGF-β, OCN, OPG, RANK, and RANKL was assessed.Immunohistochemical results showed upregulated expression of BMP2, RUNX2, ALP, TGF-β, OCN, and OPG and downregulated expression of RANK and RANKL in rats treated with SHED-seeded PMMA-HA scaffolds compared with control and defects treated with PMMA-HA only groups.SHED seeded into PMMA-HA scaffolds effectively influenced the expression of several osteogenic markers, such as BMP2, RUNX2, ALP, TGF-β, OCN, OPG, RANK, and RANKL, in alveolar bone defects. These findings indicate that the combination of SHED and PMMA-HA scaffolds could potentially become a promising regenerative alternative to autogenous bone grafting in alveolar bone defects.

Abstract Background Formononetin (FNT), a phytoestrogen, has shown osteogenic effects in ovariectomy-induced osteoporosis, but its therapeutic use is limited by poor bioavailability. This study aimed to compare the osteogenic potential of pure FNT and formononetin–piperine–phospholipid complex (FNT-PIP-PC) in OVX-induced osteoporosis and to quantify free FNT concentration in rat bone marrow. An in vivo study was conducted using an OVX-induced osteoporosis rat model. Adult female Sprague–Dawley (SD) rats were ovariectomized and treated orally with FNT or FNT-PIP-PC at 5mg/kg for 12 weeks. Therapeutic efficacy was evaluated using body composition analysis, µCT, L5 compression, bone markers, and pharmacokinetics parameters in the bone marrow via LC–ESI–MS/MS. Results FNT-PIP-PC treatment significantly restored trabecular bone volume and microarchitecture in the femur and tibia, improved uterine mass, increased osteocalcin (OCN), and reduced C-terminal telopeptide of type 1 collagen (CTX) levels. These findings aligned with enhanced mRNA expression of RUNX, RANKL, BMP2, and OPG. Additionally, FNT-PIP-PC improved pharmacokinetic parameters like C max , AUC 0-t , and AUC 0-∞ of free FNT from FNT-PIP-PC compared to pure FNT. Conclusion Oral administration of FNT through complexation with PIP reduced phase II metabolism and enhanced free FNT concentrations, leading to a significant increase in its bioavailability in bone marrow, supporting the targeted delivery. Furthermore, the FNT-PIP-PC complex demonstrated a marked improvement in the osteogenic potential of FNT on OVX-induced osteoporosis rats with no significant adverse effects. Collectively, these findings support the FNT-PIP-PC potential as a safe and effective therapeutic option for postmenopausal osteoporosis. Graphic abstract

Data on the interplay between muscle, bone, and adipose tissue metabolism in normal-weight children with Prader–Willi syndrome (PWS) undergoing growth hormone (GH) therapy and dietary interventions are limited. This study aimed to assess the myokine profile and explore the associations between myokines, bone markers, adipokines, and body composition in these patients. The study included 26 children with PWS and 26 age-matched healthy controls. Serum levels of irisin, myostatin (MSTN), fibroblast growth factor-2, insulin-like growth factor-I (IGF-I), IGF-binding protein-2, bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated OC (Gla-OC), periostin, soluble receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase 5b, leptin/soluble leptin receptor, adiponectin, and proinsulin were measured using immunoenzymatic assays. Children with PWS had significantly lower lean mass (p = 0.047) and a higher fat mass/lean mass ratio (p < 0.001) than controls. Irisin levels were lower in the PWS group (p = 0.031), while MSTN levels were similar between the groups. In patients, irisin positively correlated with BALP (p = 0.025) and negatively correlated with Gla-OC (p = 0.041) and periostin (p = 0.005). MSTN was positively associated with proinsulin (p = 0.001) and negatively associated with lean mass (p = 0.015). OC concentration was lower in the PWS group and correlated positively with lean mass (p = 0.052). Children with PWS exhibit altered myokine, osteokine, and adipokine profiles, as well as differences in body composition. Reduced irisin and osteocalcin levels, along with the negative association between MSTN and lean mass, may impair muscle development and bone metabolism. These imbalances could also contribute to future metabolic disorders in patients with PWS.

Public health problems regarding the potential association between Parkinson's disease (PD) and the increased prevalence of osteoporosis have been raised. However, the exact relationship, as well as potential treatment strategies, remains unclear and requires further investigation. Melatonin (MLT) is known for its beneficial effects on bone metabolism and its strong neuroprotective properties. Therefore, this study aimed to evaluate the potential role of MLT in the prevention and treatment of bone loss associated with PD using an hemiparkinsonian rat model induced by the destruction of dopaminergic neurons following intracerebral injection of 6-hydroxydopamine (6-OHDA). Forty male Wistar rats were divided into 5 groups: Control (CTR), 6-OHDA, MLT, 6-OHDA + MLT 1, and 6-OHDA + MLT 15. MLT (20 mg/kg/day) was administered intraperitoneally from Day 1 or Day 15, depending on the group. The effects on locomotor performance, oxidative status, bone structure, collagen accumulation, mineralization and the expression of bone marker proteins and genes were examined. Our results showed that the degeneration of dopaminergic neurons caused by 6-OHDA significantly impaired locomotor performance and induced marked alterations in bone parameters. Early MLT treatment (Day 1) mitigated these bone alterations by preserving structural integrity, enhancing collagen accumulation, and modulating bone marker expression. Importantly, beneficial effects on bone were also observed when MLT was administered later (Day 15), despite the absence of significant improvement in motor deficits. These findings suggest that dopaminergic neuron degeneration can negatively influence bone health and that MLT may exert a direct osteoprotective effect, supporting its possible therapeutic utility in managing bone fragility associated with PD.

Background. Osteoporosis is an age-related metabolic disease that has a significant impact on bone health and overall quality of life. It is gaining importance as one of major medical concerns with the rapid increase in the geriatric population in our world. The aim of the study was to determine the biochemical markers of bone and cartilage tissue metabolism in urine of patients with newly sustained compression fractures of vertebrae in adjacent and distant segments. Subjects and methods. The research was conducted at the M. I. Sytenko Institute of Spine and Joint Pathology, National Academy Medical Science of Ukraine for 2023–2025. The diagnosis of osteoporosis was confirmed using densitometry. The age of patients in group I ranged from 55 to 72 years, in the group II – from 55 to 73 years, and in the group III – from 56 to 72 years. The T-scores were as follows: Group I, −0.8±0.2; Group II, −2.63±0.3; and Group III, −2.8±0.26. Statistical analysis of the data was carried out using the software packages Microsoft Excel XP and Statsoft Statistica 6.0. Results and conclusion. In patients from Group II, who had concomitant osteoporosis compared to Group I, new vertebral compression fractures occurred following spinal surgery against the background of osteoporosis. These changes were reflected in alterations in biochemical markers of bone and cartilage tissue, including: increased levels of glycoproteins in the blood (markers of systemic inflammation), elevated chondroitin sulfates (indicating bone and cartilage degradation), increased activity of alkaline phosphatase (specifically its bone isoenzyme) and acid phosphatase (markers of bone metabolism), higher levels of ionized calcium (indicative of mineral matrix destruction), as well as enhanced urinary excretion of hydroxyproline (a marker of collagen catabolism) and uronic acids (metabolites of proteoglycans from bone and cartilage tissue). The laboratory studies conducted indicate the possibility of using a complex of biochemical markers in assessing the risks of progression of destruction of bone and cartilage tissue after fractures in patients, which may lead to the need for repeated surgical interventions.

Effects of yeast protein on the promotion of intestinal calcium absorption (in vivo/in vitro) and bone formation (in vivo) in rats fed by normal and low-calcium diets.