Journal of Bone Metabolism最新文献

Background: Calcium is essential for bone health, but its intake remains inadequate in populations with limited dairy consumption. Fish bones, abundant in calcium and phosphorus, represent a largely untapped natural resource for dietary calcium supplementation. The application of high-energy ball milling (HEM) presents a promising strategy to enhance calcium bioavailability by producing particles at the nanoscale.

Methods: This study used HEM to convert fish bones from Euthynnus affinis (tuna) and Lutjanus sp. (snapper) into nanoparticles. The resulting powder was analyzed for particle size, morphology, crystallinity, thermal, flowability, hygroscopicity, mineral composition, and proximate constituents.

Results: The HEM process successfully reduced the particle size of snapper and tuna bone powder to 729.83 and 847.93 nm, respectively, without altering their crystallinity. Morphological analysis revealed irregularly shaped particles, while thermal analysis indicated an exothermic decomposition pattern. No hygroscopic properties were observed in any of the samples. The nanonization process preserved the intrinsic mineral composition of the fish bones. Calcium/Phosphorus ratios remained >1.8. Elemental analysis confirmed high levels of calcium, phosphorus, and essential minerals such as potassium, magnesium, and sodium, while the protein and ash contents met nutritional standards.

Conclusions: Fish bone-derived nanoparticles produced via HEM exhibit advantageous physicochemical characteristics for nutraceutical applications and represent a promising source of bioavailable calcium to support bone health.

Background: The association between diet quality (DQ) and osteoarthritis (OA) among the Asian population is unclear. Even within this population, the associations between DQ and OA may differ by region. We examined the relationship between DQ and radiologic knee OA (RKOA) among Koreans, stratifying participants by residential area.

Methods: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey conducted in 2013. A total of 2,222 participants aged 50 years old and older with available data on RKOA and DQ were analyzed. DQ was evaluated using the Korean Healthy Eating Index (KHEI). RKOA was diagnosed via radiography and defined as having a Kellgren-Lawrence grade ≥2 in the knee. Participants were categorized by residential region: metropolitan cities, small to medium-sized cities, or rural areas. The odds ratios for RKOA across the three regions were analyzed using multiple logistic regression, adjusting for confounding factors.

Results: High KHEI scores were associated with lower odds of RKOA (P for trend=0.03). This association was primarily observed in residents of metropolitan cities, particularly among men (P for trend=0.02).

Conclusions: Better DQ is associated with reduced odds of RKOA in older Korean adults living in metropolitan areas.

Background: Bone mineral density (BMD) is a key predictor of fracture risk in postmenopausal women. Evidence on the influence of fat and lean mass (LM) on BMD remains contradictory. This study aimed to assess the associations between BMD at different sites (whole-body, upper, and lower limbs) and anthropometric and body composition variables measured by dual energy X-ray absorptiometry (DXA) in postmenopausal women.

Methods: A cross-sectional study was conducted on 308 healthy postmenopausal women. Anthropometric data and whole-body DXA scans were used to measure BMD, total fat mass (FM), LM, appendicular LM index (ALMI), and abdominal fat. Pearson or Spearman correlation analyses were used according to variable distribution, and a correlation matrix along with variance inflation factor analyses was used to reduce 18 variables to a final set of 5. Multiple linear regression models were built for BMD at each site.

Results: Age was negatively correlated with BMD at all sites. Total LM and ALMI demonstrated positive correlations with BMD, whereas body mass index (BMI) and abdominal fat exhibited weaker positive associations. In multivariable analyses, age was negatively associated with whole-body BMD, while total LM was positively associated. For lower-limb BMD, age and total LM were significant predictors, with BMI showing a positive but weaker association. For upper-limb BMD, total LM, and ALMI were all positively associated. The models demonstrated satisfactory fit (adjusted R², 0.341-0.438; global P<0.0001).

Conclusions: Age and total LM were independently and consistently associated with BMD in postmenopausal women, whereas FM and BMI had a limited impact.

Glucagon-like peptide-1 (GLP-1) analogs, originally developed as antidiabetic agents, have emerged as groundbreaking drugs for treating obesity, following reports of their remarkable weight-reducing effects. With growing recognition of obesity as a disease in modern society and a sharp rise in its prevalence, pharmacological interventions are now being actively pursued. However, due to their mechanism of action, primarily appetite suppression, GLP-1 analogs have been associated with various adverse effects. Most notably, muscle loss - which may be related to reduced nutritional intake - has become an important issue in the long-term management of patients undergoing GLP-1 therapy. This has drawn attention to myostatin (MSTN) inhibitors for their ability to significantly increase muscle mass. These agents are now being explored not only as a strategy to offset the side effects of GLP-1 analogs, but also as direct therapeutics for a range of metabolic disorders, including obesity and diabetes. In this review, we discuss the emerging therapeutic potential of MSTN inhibitors and examine current clinical trials investigating their use alone or in combination with GLP-1 analogs in metabolic disorders.

Background: The survival impact of bisphosphonates (BPs) remains uncertain, particularly in East Asian populations, where new-user analyses have been limited.

Methods: This was a retrospective, new-user cohort study using the Korean National Health Insurance Service-National Sample Cohort (2002-2011). We identified new users of BPs (N=41,854), and a 1:1 age-matched control group (N=41,854) among women aged ≥ 50 years. Participants were followed for all-cause mortality for up to 10 years. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs), adjusting for age and the Charlson Comorbidity Index.

Results: A total of 83,708 women were included. Compared with the control group, the risk of all-cause mortality was lower in BP group. BP users showed adjusted HR of 0.47 (95% confidence interval, 0.44-0.49; P<0.001) compared to controls.

Conclusions: In this large, nationwide Korean cohort, initiating BPs was associated with a reduced risk of all-cause mortality in women aged 50 and older. These findings suggest that BPs may have survival benefits beyond fracture prevention.

Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass and increased risk of fractures, with limitations in traditional treatment methods. The "brainbone axis" theory has revealed a bidirectional regulatory network between the central nervous system and the skeletal system, providing new insights into the mechanisms and treatment of OP. This review summarizes the bidirectional regulatory mechanisms of the "brain-bone axis", including descending pathways (such as the regulation of bone metabolism by the sympathetic nervous system, parasympathetic nervous system, and hypothalamic nuclei) and ascending feedback (such as bone-derived factors influencing central nervous system function through the blood-brain barrier), and explores the synergistic roles of endocrine systems (such as the thyroid axis and gonadal axis) within this network. Additionally, the article summarizes multi-modal treatment strategies based on the "brain-bone axis" theory, offering new insights for the precise prevention and treatment of OP. Future research should further integrate basic and clinical studies to advance the paradigm shift of OP from a localized bone disorder to a systemic disease.

Background: Posterior spinal fusion is performed for severe adolescent idiopathic scoliosis (AIS), with bone graft playing a critical role in achieving solid fusion. Iliac crest bone graft (ICBG) is the gold standard but has donor site morbidity, leading to increased use of non-ICBG. This study compared the effectiveness and safety of ICBG and non-ICBG bone grafts in AIS.

Methods: This meta-analysis included 23 studies with 3,350 patients, categorized into ICBG and non-ICBG groups. The primary outcome was fusion rate; secondary outcomes were implant-related complication rate, infection rate, donor site pain, blood loss, and operation time. A proportion meta-analysis was conducted to estimate binary outcomes, and a weighted mean model was used to estimate continuous variables.

Results: The fusion rate was 97% (95% confidence interval [CI], 93-99) in ICBG group and 97% (95% CI, 95-98) in non-ICBG group. Implant-related complications occurred in 5% (95% CI, 3-7) and 4% (95% CI, 2-6) of each group, while surgical site infections occurred in 3% (95% CI, 2-7) and 2% (95% CI, 1-3). Donor site pain was observed exclusively in ICBG group, with a prevalence of 49% (95% CI, 3-97). Estimated pooled blood loss was 1,461.10 mL (95% CI, 545.30-2,376.90) in ICBG group and 1,047.45 mL (95% CI, 666.92-1,427.99) in non-ICBG group. The estimated pooled operation time was 246.77 (95% CI, 221.74-271.80) and 232.37 (95% CI, 194.88-269.86) for each group.

Conclusions: Considering both ICBG and non-ICBG demonstrated high fusion rates and low complication rates, non-ICBG grafts may serve as an effective and safe alternative to ICBG, minimizing morbidity, donor site pain, and blood loss.

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia and osteomalacia, resulting from excessive production of fibroblast growth factor 23 by mesenchymal tumors. Although various imaging techniques are used to localize the tumor, the rarity of the disease poses significant challenges in tumor detection.

Methods: After retrospectively analyzing 25 TIO patients who visited the Severance bone and mineral clinic between 2004 and 2024, we added all reported TIO cases in Korea by searching PubMed, Embase, and Web of Science. Using the PRISMA method, an additional 14 reports comprising 22 patients were included.

Results: Among the 47 patients, 25 (53.2%) were male, with a median age of 52 years. Tumors were most commonly located in the lower extremities (57.5%), with a median size of 1.9 cm. Surgical resection, including radiofrequency ablation, was performed in 45 patients; reoperation was required in 26.7% (12/45) due to residual tumors. After gallium scans were covered by insurance, 83.3% (25/30) of patients underwent gallium-based imaging for tumor localization with 77.3% of tumors successfully localized in initial scan. Of the five patients with negative initial scans, four (80%) showed positive findings on a second scan conducted 1 to 2 years later.

Conclusions: Although gallium scans are the most commonly employed imaging modality for detecting tumors responsible for TIO, localization remains challenging due to the small tumor size, potential for widespread anatomical distribution, and prolonged diagnostic delay. Repeating gallium imaging can yield positive results in previously negative cases, and additional imaging modalities may be necessary to facilitate accurate localization.

Background: Myostatin (MSTN) is a well-known negative regulator of skeletal muscle growth, and its pharmacological blockade, such as with follistatin (FST), an endogenous MSTN inhibitor, is under active investigation as a treatment for muscle-wasting conditions. However, the dynamics of MSTN signaling during in vitro myogenesis and its modulation by culture conditions remain incompletely understood.

Methods: Primary myoblasts were isolated from wild-type (WT), Mstn-/-, and FST transgenic (F66) mice to evaluate the effects of MSTN inhibition on myotube formation. Myoblasts were differentiated on Matrigel-coated surfaces in the presence of horse serum. Myotube maturation was evaluated by confocal microscopy and reverse transcription-polymerase chain reaction; protein synthesis was assessed using a puromycin incorporation assay; and MSTN concentrations in serum were quantified by enzyme-linked immunosorbent assay.

Results: Mstn expression peaked at 24 hr of differentiation, coinciding with early myotube formation, and progressively declined as myotubes matured. Both Mstn-/- and F66 myotubes showed increased thickness and protein synthesis compared to WT controls, with more pronounced effects observed in F66 myotubes. Consistent with this, F66 myotubes also displayed higher expression of myogenic maturation markers. Notably, horse serum used in the culture medium contained detectable levels of MSTN, which may have partially restored MSTN signaling in Mstn-/- cultures and masked the full knockout phenotype.

Conclusions: FST overexpression induces greater myotube hypertrophy and protein synthesis than Mstn deletion, likely due to its broader inhibition of both endogenous and serum-derived MSTN. These findings highlight the importance of serum composition in interpreting phenotypes from in vitro knockout models targeting secreted factors such as MSTN.

The 17th Sarcopenia, Cachexia, and Wasting Disorders Conference, held from December 6 to 8, 2024, in Washington, DC, showcased groundbreaking advancements in understanding and managing muscle wasting conditions. Drawing on the lecture notes and presentations of internationally recognized experts who spoke at the meeting, this review highlights key insights and recent developments discussed during the conference. This review focuses on sarcopenia, cancer cachexia, and other wasting disorders linked to chronic diseases. Key discoveries included the identification of the Macroautophagy and YouTH Optimizer pathway in muscle regulation, the role of ectodysplasin A2 receptor-nuclear factor-κB-inducing kinase signaling in muscle atrophy, and the impact of mitochondrial dysfunction on systemic health. Advancements in diagnostic tools, including artificial intelligence-powered imaging and novel biomarkers, are transforming the detection and management of these conditions. Emerging therapeutic strategies, such as glucagon-like peptide 2-based treatments, selective androgen receptor modulators, and cytokine inhibitors, are reshaping the therapeutic landscape. The conference underscored the importance of precision medicine, integrating molecular insights with personalized care approaches, and emphasized multidisciplinary rehabilitation to optimize patient outcomes. The conference also highlighted promising clinical advancements, including the HIPGEN trial on placental-expanded stromal cells for muscle regeneration in hip fracture patients and the ponsegromab study targeting growth/differentiation factor-15 inhibition to mitigate cancer cachexia-associated muscle wasting. This review highlights the integration of basic science, innovative diagnostics, and clinical applications as a promising framework for addressing the complex challenges posed by muscle-wasting disorders. As the field progresses, these insights offer hope for improving the quality of life and survival of affected patients.