Search Results (273)

Osteoarthritis (OA) in the trapeziometacarpal joint (TM) is a prevalent form of hand OA, yet research on biomarkers specific to hand OA remains limited. This study aims to identify systemic plasma biomarkers at baseline in TM OA patients that are associated with patient-reported outcomes one year post-treatment. Blood samples and clinical data were collected prospectively from 143 TM OA patients undergoing conservative therapy, fat grafting, or surgery, with one-year follow-up. Supervised machine learning with Lasso regularization analyzed associations among 10 systemic biomarkers related to cartilage turnover, bone remodeling, pain, or lipid metabolism. Generalized estimating equation models evaluated baseline biomarker associations with one-year outcomes. Patients averaged 61 years, were mostly female (69%), and were primarily treated conservatively (47%). The machine learning model identified associations between outcomes and biomarkers, including PIIANP, Visfatin, adiponectin, and leptin. Adjusted analyses revealed baseline PIIANP associated with VAS, QuickDASH, and TASD improvements, while Visfatin correlated with VAS worsening. We could identify two different plasma markers that could predict the clinical outcome of TM OA treatment. Baseline PIIANP is associated with improvement, while Visfatin is associated with worsening in TM OA outcomes up to one year post-treatment. Further prospective studies are needed to confirm and solidify these findings. Full article

Secondary hyperparathyroidism (SHPT) in chronic kidney disease often necessitates parathyroidectomy (PTX), but this definitive treatment can precipitate hungry bone syndrome (HBS)—a profound, prolonged hypocalcemia caused by the rapid skeletal uptake of minerals after surgery. HBS results from the abrupt cessation of parathyroid hormone (PTH)-driven bone resorption while bone formation continues, leading to intensive mineral deposition (mainly calcium) into chronically demineralized bone. Clinically, HBS ranges from asymptomatic biochemical disturbances to life-threatening hypocalcemia with tetany, seizures, and/or cardiac arrhythmias. This illustrative review synthesizes current knowledge of HBS pathogenesis and management in the context of SHPT. We detail how the high-turnover bone remodeling state of SHPT (osteitis fibrosa cystica) creates an expansive unmineralized osteoid pool that avidly mineralizes post-PTX. We also explore molecular mechanisms (e.g., RANKL/OPG dysregulation, Wnt/β-catenin activation, osteocyte-driven signals, and calcium-sensing receptor effects) that underpin this process. Key preoperative risk factors for HBS include very elevated PTH and alkaline phosphatase levels, large skeletal calcium deficits, younger patient age, and total PTX. We outline the typical postoperative course of HBS, phased from immediate acute hypocalcemia to a nadir and gradual recovery. Prevention and management strategies are emphasized, centered on vigilant monitoring and aggressive calcium and calcitriol supplementation, with preoperative optimization (e.g., vitamin D loading, calcimimetics) to mitigate severity. By enhancing risk stratification and perioperative care, clinicians can improve outcomes and safely navigate patients through this challenging complication of endocrine surgery. Full article

Inflammaging has been implicated in age-related bone loss and fragility fractures through immune-mediated effects on bone turnover. We aimed to explore the relationship between systemic inflammatory markers and bone health in older adults, focusing on the differences between patients with osteoporotic fractures and non-fractured controls. We retrospectively analyzed 40 older patients (20 with hip fractures and 20 with osteoarthritis without prior fragility fractures). We compared routine inflammatory markers, including red cell distribution width (RDW), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and the composite CRP–albumin–lymphocyte index (CALLY), between groups. Bone mineral density (BMD) at the hip, lumbar spine, and wrist, as well as the FRAX score, were assessed. Correlations between inflammatory markers, BMD, and FRAX scores were evaluated using Spearman’s coefficient. Patients with fractures exhibited significantly elevated CRP (66.2 ± 70.3 vs. 3.8 ± 4.0 mg/L, p = 0.0008) and SII (1399.7 ± 1143.4 vs. 751.4 ± 400.8, p = 0.025) compared to controls. RDW, NLR, and CALLY scores did not differ significantly between the groups. Higher CRP levels were associated with lower BMD at all sites (hip: r ≈ −0.63, p = 0.002; spine: r ≈ −0.60, p = 0.005; wrist: r ≈ −0.60, p = 0.005). No significant correlations were observed between the SII and BMD or FRAX values. Elevated systemic inflammation, particularly indicated by CRP and SII, was associated with osteoporotic fracture status and low bone density in our cohort. These findings support the concept that inflammatory pathways may contribute to osteoporosis and fracture risk and suggest that inflammatory markers could serve as adjunctive tools in fracture risk assessment. Further studies are required to clarify the causality and evaluate whether targeting chronic inflammation can improve bone health in older adults. Full article

In response to the recent meta-analysis by Tassi et al. on hormonal contraception and bone metabolism, we raise critical concerns regarding the interpretation of bone turnover markers as surrogates for bone mineral density (BMD). While bone turnover markers can offer early insights into bone remodeling, they do not directly predict long-term BMD changes, which require 12–24 months to detect. The assumption that equivalent percentage changes in bone formation and resorption markers reflect stable BMD is not supported by current evidence. Bone metabolism varies significantly across life stages, particularly during adolescence and early adulthood, when peak bone mass is still accruing—underscoring the need for age-specific analyses. Additionally, biomarker interpretation is limited by assay variability, inconsistent sampling protocols, and uncertain clinical implications, especially for formation markers. Mechanistically, estrogen supports bone integrity by inhibiting resorption and promoting formation; thus, combined hormonal contraceptives (CHCs) containing estrogen may help preserve bone health. In contrast, progestin-only methods can suppress endogenous estrogen production, potentially compromising skeletal development. We advocate for longitudinal studies incorporating both BMD and turnover markers, stratified by age and contraceptive formulation, to guide safer and more informed contraceptive choices that protect long-term bone health. Full article

Background and clinical significance: Paget’s disease of bone involves anomalies of the bone metabolism; however, the presence of tumor-derivate abnormal parathyroid hormone (PTH) levels does not represent one of these disturbances. To our best knowledge, the association with normocalcemic variant of primary hyperparathyroidism has been limitedly reported, and here we introduce such an unusual overlap in a male suffering from osteoporosis. Case presentation: A 71-year-old, non-smoker man was hospitalized for mild, nonspecific dysphagia, asthenia, decreased appetite, and mild weight loss during the latest 2 months. His medical history included cardiovascular conditions and an abnormal PTH level with normal serum calcium under daily cholecalciferol supplements (tested twice during latest 12 months). The lab findings pointed out a normocalcemic primary hyperparathyroidism (PTH of maximum 163 pg/mL, and total calcium of 9.3 mg/dL) caused by a right parathyroid tumor of 1.2 cm, as confirmed by computed tomography (CT). Additionally, CT showed a left humerus lesion suggestive of Paget’s disease of bone, a confirmation that also came from the whole-body bone scintigraphy. The subject presented increased P1NP and osteocalcin, CrossLaps as bone formation, and resorption markers, with normal total alkaline phosphatase. CT scan also detected multiple vertebral fractures and small kidney stones. Zoledronate i.v. (3 mg, adjusted for creatinine clearance) was administered, taking into consideration all three bone ailments (Paget’s disease, high PTH/calcium, and osteoporosis) with further follow-up. Conclusions: This case highlights the following technical notes based on a real-life setting: 1. Despite the mentioned bone diseases, no bone pain was present. Loss of appetite, dysphagia, and asthenia may be a consequence of mineral metabolism disturbances. 2. The panel of blood bone turnover markers levels might be related to both hyperparathyroidism and Paget’s disease; notably, rare cases of Paget’s disease with normal alkaline phosphatase were prior reported. 3. A meticulous differentiation between secondary and primary hyperparathyroidism is required. In this instance, lack of hypocalcaemia and vitamin D deficiency was suggestive of the diagnosis of a primary variant. 4. Kidney stones, osteoporosis, and osteoporotic fractures may be correlated with both conditions, as well, while a dual perspective of the therapy, since the patient was not a parathyroid surgery candidate, included a first dose of zoledronate with consecutive long-term follow-up. To our best knowledge, the co-presence of normocalcemic variant of primary hyperparathyroidism represents an exceptional finding in a patient synchronously diagnosed with Pagetic lesions and osteoporosis complicated with vertebral fractures. Full article

Background/Objectives: Menopause leads to estrogen deficiency, which negatively affects bone density, skin integrity, and hair health in women. This study aimed to evaluate the effects of fish-derived collagen peptides, calcium, and vitamin D3 supplementation on body composition, bone turnover markers, skin condition, and hair loss in menopausal women. Methods: Participants were randomized into four groups: placebo (G01), 1000 mg calcium + 400 IU vitamin D3 (G02), 5 g collagen (G03), and 1000 mg calcium + 400 IU vitamin D3 + 5 g collagen (G04). Participants received daily supplementation for six months. Body composition, biochemical bone markers (P1NP, BAP, osteocalcin), skin hydration, elasticity, transepidermal water loss (TEWL), and hair loss were assessed at baseline and follow-ups. Results: No significant changes were observed in body composition or bone biomarkers including P1NP, BAP, and osteocalcin across groups. Serum creatinine, ALT, and AST levels remained within normal ranges. Serum calcium levels remained stable, and urinary calcium excretion slightly increased in calcium-supplemented groups, indicating no adverse effects on kidney or liver function. G02 and G04 exhibited slightly decreased serum calcium levels compared to G01 and G03. However, G04 showed significantly improved skin hydration by 23% and skin elasticity by 8.52% compared to baseline after six months, whereas the placebo group showed negligible changes. G03 also showed notable improvement in elasticity by 12.23%, indicating collagen’s dominant role. The G02, G03, and G04 also significantly retarded hair shedding compared to the placebo (G01) group. TEWL did not significantly change in any group. Conclusions: These findings suggest that six-month supplementation with collagen peptides, particularly when combined with calcium and vitamin D, improves skin hydration and elasticity in menopausal women. Full article

Background/Objectives: Dairy and soybean are important potential dietary sources of bone health. However, their comparative effectiveness and the role of specific components remain unclear. In this network meta-analysis (NMA), we aimed to compare the effects of various dairy and soy products (food level) and their key bioactive components (component level) on bone health in healthy women. Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science (up to 28 February 2025) for randomized controlled trials. A frequentist random-effects NMA was used to compare interventions for lumbar spine (LS) and total body (TB) bone mineral density (BMD) and bone turnover markers [osteocalcin (OC), deoxypyridinoline (DPD)]. Mean differences (MDs) and 95% confidence intervals were pooled. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA). Results: Sixty RCTs involving 6284 participants (mean age: 54.2 years) were included. At the food level, no dairy or soy interventions significantly improved outcomes versus control, although milk + yogurt ranked numerically highest based on SUCRA values. At the bioactive-component level, the combination of casein + whey protein (MD 0.04 g/cm², 95% CI 0.01–0.06) and soybean protein (MD: 0.03 g/cm², 95% CI: 0.01–0.05) significantly increased TB BMD. Whey protein alone (SUCRA 74.4% for LS BMD) and casein + whey protein (SUCRA 86.3% for TB BMD and 75.9% for DPD) were among the highest-ranked interventions for bone health. Conclusions: The combination of milk and yogurt may be relatively promising among dairy products for bone health. Whey protein appears to be a key bioactive component beneficial for women’s bone health. Full article

Background/Objectives: Fructooligosaccharides (FOS) and dried tart cherry (TC) are examples of simple and complex (i.e., within a food matrix) prebiotics that have demonstrated promising osteoprotective activity. In this study, we examined how dietary supplementation with TC or FOS shapes the gut-bone axis to promote bone accrual in young adult mice, and the role of the gut microbiota in mediating these responses. Methods: Studies were performed using 10-wk-old female C57BL/6 mice (n = 10–12/group) fed a control diet or control diet supplemented with 10% TC or FOS for 10 wks alone or in combination with an antibiotic/anti-fungal cocktail to suppress the gut microbiota. The bone phenotype was characterized by dual-energy X-ray absorptiometry, micro-computed tomography and static and dynamic bone histomorphometry. The gut-microbiota was profiled and short chain fatty acids (SCFA) were assessed based on 16S rRNA profiling and gas chromatographic techniques, respectively. Results: FOS and TC enhanced bone structure, with FOS yielding more pronounced benefits across cortical and trabecular compartments. These skeletal improvements with FOS occurred in the absence of systemic changes in bone turnover markers but were accompanied by increases in local bone formation, osteoblast and osteocyte numbers, and bone mineralization in the femur. Both diets altered gut microbiota composition and increased fecal concentrations of the most abundant SCFAs (i.e., acetate, propionate and butyrate), but the response was greater with FOS. Suppression of the gut microbiota and fecal SCFAs with the antibiotic/anti-fungal cocktail inhibited the effects of FOS and TC on cortical bone, but induced unexpected improvements in the trabecular bone. Conclusions: These findings demonstrate differential effects of simple and complex prebiotics on the gut-bone axis in young adult female mice and support a role for SCFA in the cortical bone response, but not in the trabecular bone response with this model of gut microbiota suppression. Full article

Type 2 diabetes mellitus (T2DM) is known to increase the risk of fragility fractures; however, the underlying mechanism is still elusive. Reduced miR-155 and elevated RHOA are known to drive bone resorption, but their role in T2DM remains unclear. This study investigates bone remodeling imbalances in T2DM through miR-155 and RHOA expression profiling. Three-month-old female Wistar rats were fed a high-calorie diet for 3 weeks, followed by intraperitoneal injections of two lower doses of streptozotocin at weekly intervals to induce T2DM. Bone analysis from diabetic rats tested using qRT-PCR showed significantly reduced miR-155 levels and elevated RHOA. Histological analysis showed a 12.65% increase in Tb.Sp, 10.07% decrease in Tb.Th, and significant increase (p < 0.05) in apoptotic osteocytes. The bone turnover marker CTx-1 level was increased by 20.84%, and RANKL levels were significantly increased in T2DM. IL-1β and TNF-α were increased in T2DM. Bone resorption is more likely to occur in T2DM as both IL-1β and TNF-α work synergistically to promote osteoclastogenesis. MiR-155 could be an important modulator of bone remodeling in T2DM and a potential therapeutic target for diabetic osteopathy. Full article

Osteosarcopenia, characterized by concurrent bone loss and muscle wasting, significantly impacts mobility and quality of life. While age-related primary osteosarcopenia is well-studied, secondary osteosarcopenia (SOS) caused by chronic diseases remains poorly understood, particularly in young individuals. The present study aimed to comprehensively characterize musculoskeletal alterations associated with SOS using a juvenile porcine model of cerulein-induced chronic pancreatitis. Femoral bone analysis included densitometry, mechanical testing, histomorphometry, and serum bone turnover markers. The quadriceps femoris muscle was evaluated through histological analysis and gene expression profiling of antioxidant enzymes and apoptotic regulators. Animals with SOS showed significantly reduced femoral BMD compared to controls, with altered cortical geometry and compromised mechanical properties. Trabecular bone analysis revealed classic osteoporotic changes with decreased bone volume fraction. Negative changes were also observed in the growth plate morphology, indicating impaired endochondral ossification. Bone turnover markers indicated elevated bone resorption and altered formation. Muscle analysis demonstrated sarcopenic changes with selective atrophy of fast-twitch type II fibers and increased fiber density. At the molecular level, SOS muscles exhibited downregulated expression of CAT and CASP3, suggesting muscle atrophy predominantly mediated by oxidative stress and caspase-independent proteolysis rather than classical apoptosis. In conclusion, chronic pancreatitis in young pigs induces coupled bone and muscle degeneration consistent with secondary osteosarcopenia, demonstrating that muscle–bone crosstalk dysfunction occurs early in chronic inflammatory disease. Full article

Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article

Background/Objective: In patients with acute lymphoblastic leukemia (ALL), it has been demonstrated that the treatment has a negative effect on bone health. The n-3 polyunsaturated fatty acids (LCPUFAs-ω3) may attenuate bone resorption. We evaluated the effects of LCPUFAs-ω3, vitamin D, and calcium supplementation on bone turnover markers and changes in vitamin D concentrations during 6 weeks of supplementation and during 6 weeks of post-intervention follow-up in pediatric patients with ALL. Methods: Thirty-six pediatric patients with ALL were randomly assigned to the ω-3VDCa group (100 mg/kg/d LCPUFAs-ω3 + 4000 IU vitamin D + 1000 mg calcium) or the VDCa group (4000 IU vitamin D + 1000 mg calcium) for 6 weeks. Blood samples were collected to determine 25(OH)D, PTH, ICTP, and TRAP-5b (biomarkers of bone resorption) and osteocalcin (OC, a biomarker of bone production) levels at baseline, 6 weeks, and 12 weeks after supplementation. The 25(OH)D analysis was performed using ultra-high-performance liquid chromatography coupled to a mass spectrometer, and PTH and bone turnover markers were measured by ELISA. Results: The 25(OH)D concentration increased in both groups (ω3VDCa group: 19.4 ng/mL vs. 44.0 ng/mL, p < 0.0001; VDCa group: 15.3 ng/mL vs. 42.8 ng/mL, p = 0.018) and remained significantly higher at 12 weeks. At 12 weeks, ICTP showed lower concentrations in the ω-3VDCa group than in the VDCa group (0.74 ng/mL vs. 1.05 ng/mL, p = 0.024). Conclusions: Combined omega-3 and 4000 IU vitamin D supplementation for 6 weeks had a positive effect on bone health, as indicated by serum ICTP, with no effect on serum 25(OH)D levels over vitamin D supplementation alone. Full article

Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m²; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article

Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects. Full article